523 results on '"Schwann cell proliferation"'
Search Results
2. How miRNAs Regulate Schwann Cells during Peripheral Nerve Regeneration—A Systemic Review.
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Borger, Anton, Stadlmayr, Sarah, Haertinger, Maximilian, Semmler, Lorenz, Supper, Paul, Millesi, Flavia, and Radtke, Christine
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- *
NERVOUS system regeneration , *PERIPHERAL nervous system , *PERIPHERAL nerve injuries , *MICRORNA , *NON-coding RNA , *SCHWANN cells - Abstract
A growing body of studies indicate that small noncoding RNAs, especially microRNAs (miRNA), play a crucial role in response to peripheral nerve injuries. During Wallerian degeneration and regeneration processes, they orchestrate several pathways, in particular the MAPK, AKT, and EGR2 (KROX20) pathways. Certain miRNAs show specific expression profiles upon a nerve lesion correlating with the subsequent nerve regeneration stages such as dedifferentiation and with migration of Schwann cells, uptake of debris, neurite outgrowth and finally remyelination of regenerated axons. This review highlights (a) the specific expression profiles of miRNAs upon a nerve lesion and (b) how miRNAs regulate nerve regeneration by acting on distinct pathways and linked proteins. Shedding light on the role of miRNAs associated with peripheral nerve regeneration will help researchers to better understand the molecular mechanisms and deliver targets for precision medicine. [ABSTRACT FROM AUTHOR]
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- 2022
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3. Schwann cell proliferation of the cecal appendix: Intramucosal variant.
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Arredondo Montero J and Guarch Troyas R
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- Humans, Appendiceal Neoplasms pathology, Appendiceal Neoplasms diagnosis, Male, Female, Intestinal Mucosa pathology, Middle Aged, Appendix pathology, Schwann Cells pathology, Cell Proliferation
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- 2024
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4. How miRNAs Regulate Schwann Cells during Peripheral Nerve Regeneration—A Systemic Review
- Author
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Anton Borger, Sarah Stadlmayr, Maximilian Haertinger, Lorenz Semmler, Paul Supper, Flavia Millesi, and Christine Radtke
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Schwann cell proliferation ,Schwann cell migration ,Wallerian degeneration ,myelination ,biomarker nerve injury ,expression profile microRNA ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
A growing body of studies indicate that small noncoding RNAs, especially microRNAs (miRNA), play a crucial role in response to peripheral nerve injuries. During Wallerian degeneration and regeneration processes, they orchestrate several pathways, in particular the MAPK, AKT, and EGR2 (KROX20) pathways. Certain miRNAs show specific expression profiles upon a nerve lesion correlating with the subsequent nerve regeneration stages such as dedifferentiation and with migration of Schwann cells, uptake of debris, neurite outgrowth and finally remyelination of regenerated axons. This review highlights (a) the specific expression profiles of miRNAs upon a nerve lesion and (b) how miRNAs regulate nerve regeneration by acting on distinct pathways and linked proteins. Shedding light on the role of miRNAs associated with peripheral nerve regeneration will help researchers to better understand the molecular mechanisms and deliver targets for precision medicine.
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- 2022
- Full Text
- View/download PDF
5. FOSL1 modulates Schwann cell responses in the wound microenvironment and regulates peripheral nerve regeneration.
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Chen Q, Zhang L, Zhang F, and Yi S
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- Nerve Regeneration physiology, Peripheral Nerves metabolism, Animals, Rats, Rats, Sprague-Dawley, Peripheral Nerve Injuries genetics, Peripheral Nerve Injuries metabolism, Schwann Cells metabolism
- Abstract
Peripheral glial Schwann cells switch to a repair state after nerve injury, proliferate to supply lost cell population, migrate to form regeneration tracks, and contribute to the generation of a permissive microenvironment for nerve regeneration. Exploring essential regulators of the repair responses of Schwann cells may benefit the clinical treatment for peripheral nerve injury. In the present study, we find that FOSL1, a AP-1 member that encodes transcription factor FOS Like 1, is highly expressed at the injured sites following peripheral nerve crush. Interfering FOSL1 decreases the proliferation rate and migration ability of Schwann cells, leading to impaired nerve regeneration. Mechanism investigations demonstrate that FOSL1 regulates Schwann cell proliferation and migration by directly binding to the promoter of EPH Receptor B2 (EPHB2) and promoting EPHB2 transcription. Collectively, our findings reveal the essential roles of FOSL1 in regulating the activation of Schwann cells and indicate that FOSL1 can be targeted as a novel therapeutic approach to orchestrate the regeneration and functional recovery of injured peripheral nerves., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2023
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6. Dysregulated miR-29a-3p/PMP22 Modulates Schwann Cell Proliferation and Migration During Peripheral Nerve Regeneration
- Author
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Qi Chen, Yinying Shen, Yunsong Zhang, Sailing Chen, Sheng Yi, and Zhangchun Cheng
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Neuroscience (miscellaneous) ,Schwann cell ,Biology ,Schwann cell proliferation ,Rats, Sprague-Dawley ,Cellular and Molecular Neuroscience ,Cell Movement ,Peripheral myelin protein 22 ,microRNA ,medicine ,Animals ,Cell Proliferation ,Regeneration (biology) ,Sciatic nerve injury ,medicine.disease ,Sciatic Nerve ,Phenotype ,Nerve Regeneration ,Rats ,Cell biology ,MicroRNAs ,medicine.anatomical_structure ,nervous system ,Neurology ,Peripheral nerve injury ,Schwann Cells ,Myelin Proteins - Abstract
Schwann cells switch to a repair phenotype following peripheral nerve injury and create a favorable microenvironment to drive nerve repair. Many microRNAs (miRNAs) are differentially expressed in the injured peripheral nerves and play essential roles in regulating Schwann cell behaviors. Here, we examine the temporal expression patterns of miR-29a-3p after peripheral nerve injury and demonstrate significant up-regulation of miR-29a-3p in injured sciatic nerves. Elevated miR-29a-3p inhibits Schwann cell proliferation and migration, while suppressed miR-29a-3p executes reverse effects. In vivo injection of miR-29a-3p agomir to rat sciatic nerves hinders the proliferation and migration of Schwann cells, delays the elongation and myelination of axons, and retards the functional recovery of injured nerves. Mechanistically, miR-29a-3p modulates Schwann cell activities via negatively regulating peripheral myelin protein 22 (PMP22), and PMP22 extensively affects Schwann cell metabolism. Our results disclose the vital role of miR-29a-3p/PMP22 in regulating Schwann cell phenotype following sciatic nerve injury and shed light on the mechanistic basis of peripheral nerve regeneration.
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- 2021
7. Controlled release of ciliary neurotrophic factor from bioactive nerve grafts promotes nerve regeneration in rats with facial nerve injuries
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Bingran Xie, Chenlong Liao, Fukai Ma, Xiaosheng Yang, Hanming Wang, Wenchuan Zhang, Yiwei Wu, and Yi Li
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Pathology ,medicine.medical_specialty ,Materials science ,Biomedical Engineering ,Sensory system ,Ciliary neurotrophic factor ,Schwann cell proliferation ,Biomaterials ,medicine ,Animals ,Ciliary Neurotrophic Factor ,Facial Nerve Injuries ,biology ,Regeneration (biology) ,Metals and Alloys ,Functional recovery ,Facial nerve injury ,Controlled release ,Facial nerve ,Axons ,Nerve Regeneration ,Rats ,Facial Nerve ,Delayed-Action Preparations ,Ceramics and Composites ,biology.protein - Abstract
It is critical to repair severed facial nerves, as lack of treatment may cause long-term motor and sensory impairments. Ciliary neurotrophic factor (CNTF) plays an important role in terms of enhancing nerve axon regrowth and maturation during peripheral nerve regeneration after injury. However, simple application of CNTF to the transected nerve site does not afford functional recovery, because it is rapidly flushed away by bodily fluids. The aim of the present study was the construction of a new, bioactive composite nerve graft facilitating persistent CNTF delivery to aid the reconstruction of facial nerve defects. The in vitro study showed that the bioactive nerve graft generated sustainable CNTF release for more than 25 days. The bioactive nerve graft was then transplanted into the injury sites of rat facial nerves. At 6 and 12 weeks post-transplantation, functional and histological analyses showed that the bioactive nerve graft featuring immobilized CNTF significantly enhanced nerve regeneration in terms of both axonal outgrowth and Schwann cell proliferation in the rat facial nerve gap model, compared to a collagen tube with adsorbed CNTF that initially released high levels of CNTF. The bioactive nerve graft may serve as novel, controlled bioactive release therapy for facial nerve regeneration.
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- 2021
8. Claudin 14/15 play important roles in early wallerian degeneration after rat sciatic nerve injury
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Min Cai, Bryant Yung, Yi Wang, Jian-Nan Li, Huanhuan Zhang, Yuting Li, Dengbing Yao, and Jian Shao
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MAPK/ERK pathway ,Wallerian degeneration ,Medicine (General) ,Sciatic nerve ,Biology ,Schwann cell proliferation ,03 medical and health sciences ,0302 clinical medicine ,R5-920 ,Peripheral Nerve Injuries ,medicine ,Animals ,Orthopedics and Sports Medicine ,Schwann cells ,Claudin ,Protein kinase B ,Tight junctions ,030222 orthopedics ,030208 emergency & critical care medicine ,Sciatic nerve injury ,medicine.disease ,Claudin 14/15 ,Rats ,Cell biology ,Nerve regeneration ,Claudins ,Peripheral nerve injury ,Original Article ,Surgery - Abstract
Purpose Wallerian degeneration (WD) is an antegrade degenerative process distal to peripheral nerve injury. Numerous genes are differentially regulated in response to the process. However, the underlying mechanism is unclear, especially the early response. We aimed at investigating the effects of sciatic nerve injury on WD via CLDN 14/15 interactions in vivo and in vitro. Methods Using the methods of molecular biology and bioinformatics analysis, we investigated the molecular mechanism by which claudin 14/15 participate in WD. Our previous study showed that claudins 14 and 15 trigger the early signal flow and pathway in damaged sciatic nerves. Here, we report the effects of the interaction between claudin 14 and claudin 15 on nerve degeneration and regeneration during early WD. Results It was found that claudin 14/15 were upregulated in the sciatic nerve in WD. Claudin 14/15 promoted Schwann cell proliferation, migration and anti-apoptosis in vitro. PKCα, NT3, NF2, and bFGF were significantly upregulated in transfected Schwann cells. Moreover, the expression levels of the β-catenin, p-AKT/AKT, p-c-jun/c-jun, and p-ERK/ERK signaling pathways were also significantly altered. Conclusion Claudin 14/15 affect Schwann cell proliferation, migration, and anti-apoptosis via the β-catenin, p-AKT/AKT, p-c-jun/c-jun, and p-ERK/ERK pathways in vitro and in vivo. The results of this study may help elucidate the molecular mechanisms of the tight junction signaling pathway underlying peripheral nerve degeneration.
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- 2021
9. Loc680254 regulates Schwann cell proliferation through Psrc1 and Ska1 as a <scp>microRNA</scp> sponge following sciatic nerve injury
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Yanping Chen, Jiancheng Wu, Xiaosong Gu, Yaxian Wang, Yan Lu, Bin Yu, Xin-Peng Dun, Qihui Wang, Xuemin Cao, Wei Feng, and Chun Yao
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0301 basic medicine ,Chromosomal Proteins, Non-Histone ,Biology ,Schwann cell proliferation ,Rats, Sprague-Dawley ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Peripheral Nerve Injuries ,medicine ,Animals ,Axon ,Cell Proliferation ,Cell growth ,Regeneration (biology) ,Cell cycle ,Sciatic nerve injury ,Phosphoproteins ,medicine.disease ,Sciatic Nerve ,Axons ,Nerve Regeneration ,Rats ,Cell biology ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,Neurology ,Peripheral nerve injury ,RNA, Long Noncoding ,Schwann Cells ,Sciatic nerve ,030217 neurology & neurosurgery - Abstract
Peripheral nerve injury triggers sequential phenotype alterations in Schwann cells, which are critical for axonal regeneration. Long noncoding RNAs (lncRNAs) are long transcripts without obvious coding potential. It has been reported that lncRNAs participate in diverse biological processes and diseases. However, the role of lncRNA in Schwann cells and peripheral nerve regeneration is unclear. Here, we identified an lncRNA, loc680254, which is upregulated in rat sciatic nerve after peripheral nerve injury. The loc680254 knockdown inhibits Schwann cell proliferation, enhances apoptosis, and hinders cell cycle, while loc680254 overexpression has the opposite effect. Mechanically, we found that loc680254 might act as a microRNA sponge to regulate the expression of mitosis-related gene, spindle and kinetochore associated complex subunit 1 (Ska1) and proline/serine-rich coiled-coil 1 (Psrc1). Silencing of Psrc1 or Ska1 attenuates the effect of loc680254 overexpression on Schwann cell proliferation. Finally, we repaired the rat sciatic nerve gap with chitosan scaffolds loaded with loc680254-overexpressing Schwann cells and evaluated axon regeneration and functional recovery. Our results indicated that loc680254 is a new potential modulator for Schwann cell proliferation, which could be targeted to develop novel therapeutic strategies for peripheral nerve repair.
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- 2021
10. Neuroimmunophilin Ligands Accelerate and Promote Nerve Regeneration in the Rat Peripheral Nerve and Spinal Cord : Role of the Steroid Receptor—FKBP52 Complex
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Gold, Bruce G., Borlongan, Cesario V., editor, Isacson, Ole, editor, and Sanberg, Paul R., editor
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- 2003
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11. YAP and TAZ regulate Schwann cell proliferation and differentiation during peripheral nerve regeneration
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Sophie Belin, Yannick Poitelon, Abigail Hellman, Leandro N. Marziali, Jacob Herron, Ashley M. Kopec, Urja Bhatia, Haley Jeanette, and Maria Laura Feltri
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0301 basic medicine ,Taz ,research Article ,Schwann cell ,Cell Cycle Proteins ,Biology ,Schwann cell proliferation ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Myelin ,Mice ,0302 clinical medicine ,medicine ,Animals ,Hippo Signaling Pathway ,Remyelination ,Research Articles ,Adaptor Proteins, Signal Transducing ,Cell Proliferation ,Hippo signaling pathway ,Regeneration (biology) ,Cell Differentiation ,Nerve injury ,Cell biology ,Nerve Regeneration ,myelin ,030104 developmental biology ,medicine.anatomical_structure ,Neurology ,nervous system ,Myelin maintenance ,nerve injury ,Yap ,Schwann Cells ,medicine.symptom ,030217 neurology & neurosurgery - Abstract
YAP and TAZ are effectors of the Hippo pathway that controls multicellular development by integrating chemical and mechanical signals. Peripheral nervous system development depends on the Hippo pathway. We previously showed that loss of YAP and TAZ impairs the development of peripheral nerve as well as Schwann cell myelination. The role of the Hippo pathway in peripheral nerve regeneration has just started to be explored. After injury, Schwann cells adopt new identities to promote regeneration by converting to a repair‐promoting phenotype. While the reprogramming of Schwann cells to repair cells has been well characterized, the maintenance of such repair phenotype cannot be sustained for a very long period, which limits nerve repair in human. First, we show that short or long‐term myelin maintenance is not affected by defect in YAP and TAZ expression. Using crush nerve injury and conditional mutagenesis in mice, we also show that YAP and TAZ are regulators of repair Schwann cell proliferation and differentiation. We found that YAP and TAZ are required in repair Schwann cells for their redifferentiation into myelinating Schwann cell following crush injury. In this present study, we describe how the Hippo pathway and YAP and TAZ regulate remyelination over time during peripheral nerve regeneration., Main Points YAP and TAZ are required for Schwann cells dedifferentiation, proliferation, and remyelination after peripheral nerve crush injury.
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- 2020
12. Molecular mechanism of microRNA-21 promoting Schwann cell proliferation and axon regeneration during injured nerve repair
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Qun Gao, Lu Xinhua, Luo Juncheng, Chuan Chen, Zhangyu Li, Xinjie Ning, and Hui Wang
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Male ,Neurogenesis ,Gene Expression ,Schwann cell ,Apoptosis ,Biology ,Transfection ,Schwann cell proliferation ,03 medical and health sciences ,0302 clinical medicine ,Genes, Reporter ,Peripheral Nerve Injuries ,Ganglia, Spinal ,microRNA ,medicine ,Animals ,Axon ,Molecular Biology ,Cells, Cultured ,Cell Proliferation ,030304 developmental biology ,Neurons ,0303 health sciences ,Regeneration (biology) ,Cell Biology ,Nerve injury ,Axons ,Nerve Regeneration ,Rats ,Cell biology ,Disease Models, Animal ,MicroRNAs ,medicine.anatomical_structure ,Gene Expression Regulation ,030220 oncology & carcinogenesis ,Peripheral nerve injury ,Molecular mechanism ,Schwann Cells ,medicine.symptom ,Biomarkers ,Research Paper - Abstract
At present, the functional recovery after nerve injury is not satisfactory in clinical practice. The aim of this study was to explore the molecular mechanism of miR-21 promoting Schwann cells (SC) proliferation and axon regeneration after peripheral nerve injury, providing a theoretical basis for injured nerve repair. Nerve injury models were constructed to determine the expression of miR-21 in the injured nerve by Quantitative Real-Time PCR (qRT-PCR). After miR-21 over-expression SC (mimic-miR-21) group, control SC (control-miR-21) group and blank SC (RSC96) group were constructed, SC proliferation was determined by CCK-8, cell cycle was analysed by flow cytometry, dorsal root ganglion neuron (DRGn) axon regeneration was observed after DRGn was cultured with SCs for 7 days, the expressions of TGFβI, TIMP3, EPHA4 as well as apoptosis-related proteins caspase-3 and caspase-9 were detected by qRT-PCR and Western blot in the three groups, respectively. Target genes were confirmed by dual-luciferase reporter gene assay. The expressions of TGFβI, TIMP3 and EPHA4 were assessed by immunofluorescence in vivo. qRT-PCR indicated that miR-21 expression was significantly higher in the model group than in the sham operation and blank groups. SC proliferation index (PI) was significantly higher, the apoptosis rate was significantly lower, the axon was significantly longer, and mRNA and protein expressions of TGFβI, TIMP3, EPHA4 as well as apoptosis-related proteins caspase-3 and caspase-9 were significantly lower in the mimic-miR-21 group than in the control-miR-21 and RSC96 groups. The double luciferase assay confirmed that TGFβI, TIMP3 and EPHA4 were potential target genes of miR-21. In vivo immunofluorescence also indicated that expressions of TGFβI, TIMP3, EPHA4 were lower in the mimic-miR-21 group than in the control-miR-21 and RSC96 groups. We conclude that during injured peripheral nerve repair, miRNA-21 plays an important role in promoting SC proliferation and axon regeneration by regulating TGFβI, TIMP3 and EPHA4 target genes.
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- 2020
13. Microtopographical patterns promote different responses in fibroblasts and Schwann cells: A possible feature for neural implants
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Anthony B. Brennan, Cary A. Kuliasha, Syed-Mustafa Jamal, Nicole A Bohmann, Sahba Mobini, Jack W. Judy, Christine E. Schmidt, Zachary A. Siders, and Defense Advanced Research Projects Agency (US)
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Cell type ,Materials science ,Neural Prostheses ,0206 medical engineering ,Cell ,Biomedical Engineering ,Schwann cell ,02 engineering and technology ,Bacterial Adhesion ,Article ,Cell Line ,Schwann cell proliferation ,Biomaterials ,In vivo ,Foreign body reaction ,Cell Adhesion ,medicine ,Animals ,Schwann cells ,Fibroblast ,Cytoskeleton ,Cell Proliferation ,Metals and Alloys ,in vitro ,Equipment Design ,Fibroblasts ,021001 nanoscience & nanotechnology ,020601 biomedical engineering ,Axons ,In vitro ,Nerve Regeneration ,Rats ,Cell biology ,Brain implant ,medicine.anatomical_structure ,Microchannel ,Ceramics and Composites ,Microtopography ,Sharklet™ ,Neural interfaces ,0210 nano-technology - Abstract
The chronic reliability of bioelectronic neural interfaces has been challenged by foreign body reactions (FBRs) resulting in fibrotic encapsulation and poor integration with neural tissue. Engineered microtopographies could alleviate these challenges by manipulating cellular responses to the implanted device. Parallel microchannels have been shown to modulate neuronal cell alignment and axonal growth, and Sharklet™ microtopographies of targeted feature sizes can modulate bio-adhesion of an array of bacteria, marine organisms, and epithelial cells due to their unique geometry. We hypothesized that a Sharklet™ micropattern could be identified that inhibited fibroblasts partially responsible for FBR while promoting Schwann cell proliferation and alignment. in vitro cell assays were used to screen the effect of Sharklet™ and channel micropatterns of varying dimensions from 2 to 20 μm on fibroblast and Schwann cell metrics (e.g., morphology/alignment, nuclei count, metabolic activity), and a hierarchical analysis of variance was used to compare treatments. In general, Schwann cells were found to be more metabolically active and aligned than fibroblasts when compared between the same pattern. 20 μm wide channels spaced 2 μm apart were found to promote Schwann cell attachment and alignment while simultaneously inhibiting fibroblasts and warrant further in vivo study on neural interface devices. No statistically significant trends between cellular responses and geometrical parameters were identified because mammalian cells can change their morphology dependent on their environment in a manner dissimilar to bacteria. Our results showed although surface patterning is a strong physical tool for modulating cell behavior, responses to micropatterns are highly dependent on the cell type., Defense Advanced Research Projects Agency, Grant/Award Number: HR0011-15-2-0030
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- 2020
14. Fabrication and in vitro evaluation of 3D composite scaffold based on collagen/hyaluronic acid sponge and electrospun polycaprolactone nanofibers for peripheral nerve regeneration
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Masoumeh Haghbin Nazarpak, Masoumeh Firouzi, Mehdi Shafieian, Zahra Hassannejad, Elahe Entekhabi, and Haniye Mohammadi
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Materials science ,Polyesters ,0206 medical engineering ,Nanofibers ,Biomedical Engineering ,Schwann cell ,02 engineering and technology ,Schwann cell proliferation ,Biomaterials ,chemistry.chemical_compound ,Dorsal root ganglion ,Hyaluronic acid ,medicine ,Animals ,Rats, Wistar ,Cells, Cultured ,Cell Proliferation ,Tissue Engineering ,Tissue Scaffolds ,biology ,Metals and Alloys ,021001 nanoscience & nanotechnology ,biology.organism_classification ,020601 biomedical engineering ,Nerve Regeneration ,Sponge ,medicine.anatomical_structure ,chemistry ,Nanofiber ,Polycaprolactone ,Ceramics and Composites ,Biophysics ,Schwann Cells ,Sciatic nerve ,0210 nano-technology - Abstract
Replacement of peripheral nerve autografts with tissue engineered nerve grafts will potentially resolve the lack of nerve tissue especially in patients with severe concomitant soft tissue injuries. This study attempted to fabricate a tissue engineered nerve graft composed of electrospun PCL conduit filled with collagen-hyaluronic acid (COL-HA) sponge with different COL-HA weight ratios including 100:0, 98:2, 95:5 and 90:10. The effect of HA addition on the sponge porosity, mechanical properties, water absorption and degradation rate was assessed. A good cohesion between the electrospun PCL nanofibers and COL-HA sponges were seen in all sponges with different HA contents. Mechanical properties of PCL nanofibrous layer were similar to the rat sciatic nerve; the ultimate tensile strength was 2.23 ± 0.35 MPa at the elongation of 35%. Additionally, Schwann cell proliferation and morphology on three dimensional (3D) composite scaffold were evaluated by using MTT and SEM assays, respectively. Rising the HA content resulted in higher water absorption as well as greater pore size and porosity, while a decrease in Schwann cell proliferation compared to pure collagen sponge, although reduction in cell proliferation was not statistically significant. The lower Schwann cell proliferation on the COL-HA was attributed to the greater degradation rate and pore size of the COL-HA sponges. Also, dorsal root ganglion assay showed that the engineered 3D construct significantly increases axon growth. Taken together, these results suggest that the fabricated 3D composite scaffold provide a permissive environment for Schwann cells proliferation and maturation and can encourage axon growth.
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- 2020
15. Exendin-4 Promotes Schwann Cell Proliferation and Migration via Activating the Jak-STAT Pathway after Peripheral Nerve Injury
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Menghan Cao, Xuanxiang Luo, Bu Xiangbo, Hu Feng, Gao Xiao, Feng Yuan, Li Jing, Li Zi'ang, Tianqun Huo, Bin Pan, Kaijin Guo, and Youzhong Hu
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0301 basic medicine ,Microarray analysis techniques ,General Neuroscience ,Regeneration (biology) ,digestive, oral, and skin physiology ,JAK-STAT signaling pathway ,Biology ,Sciatic Nerve ,In vitro ,Nerve Regeneration ,Schwann cell proliferation ,Cell biology ,03 medical and health sciences ,fluids and secretions ,030104 developmental biology ,0302 clinical medicine ,Peripheral Nerve Injuries ,Peripheral nerve injury ,Exenatide ,Humans ,Schwann Cells ,Sciatic nerve ,Signal transduction ,030217 neurology & neurosurgery ,Cell Proliferation - Abstract
Peripheral nerve injury (PNI) is a common clinical disease that causes the partial loss of segmental exercise and sensory and autonomic nervous function, placing a heavy burden on patients and their families. A previous study confirmed that exendin-4 can effectively improve nerve regeneration and functional recovery after PNI. However, the specific mechanisms by which exendin-4-mediates this repair have not been clarified. To explore the mechanism of exendin-4 in the treatment of PNI, we used microarray analysis to detect gene expression in the distal segment of the sciatic nerve after sciatic injury. Bioinformatics analyses were used to predict the roles of differentially expressed genes (DEGs) in nerve damage repair. Schwann cells (SCs) were cultured, and we verified the molecular mechanism of exendin-4 in SCs and the effect of exendin-4 on peripheral nerve regeneration through in vitro molecular biology and cell biology experiments. In vivo, exendin-4 could significantly promote peripheral nerve regeneration. A total of 180 DEGs between the exendin-4 group and the control group were detected. Bioinformatics analysis indicated that these DEGs were mainly enriched in the Jak-STAT signaling pathway. In vitro, exendin-4 could significantly promote the proliferation and migration of SCs by activating the Jak-STAT pathway, which promoted peripheral nerve regeneration. Our results indicate that exendin-4 promotes SC proliferation, migration and nerve regeneration after PNI by activating the Jak-STAT pathway. Our findings provide a basis and direction for further elucidation of the mechanisms of exendin-4 in the repair of PNI and provide a new way to treat PNI.
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- 2020
16. Exosomes derived from differentiated Schwann cells inhibit Schwann cell migration via microRNAs
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Yoon Kyung Shin, Hwan Tae Park, and Eun Jung Sohn
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0301 basic medicine ,Gene Expression ,Biology ,Exosomes ,Schwann cell proliferation ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,microRNA ,Animals ,Cells, Cultured ,General Neuroscience ,High-Throughput Nucleotide Sequencing ,Schwann cell migration ,Microvesicles ,Rats ,Antisense RNA ,Cell biology ,MicroRNAs ,030104 developmental biology ,nervous system ,Dopaminergic synapse ,Schwann Cells ,Schwann cell differentiation ,Signal transduction ,030217 neurology & neurosurgery - Abstract
Exosomes derived from Schwann cells have been known to have a variety of functions in the development and repair of the peripheral nervous system, and cyclic AMP (cAMP) is a key inducer of Schwann cell differentiation. In the present study, we aimed to study the effect of exosomes derived from differentiated Schwann cells on the expression of microRNAs (miRNAs). To show that miRNAs were altered from exosomes derived from Schwann cells, we conducted next-generation sequencing (NGS) arrays with exosomes derived from cAMP-induced differentiated Schwann cells and control. NGS arrays revealed that 22 miRNAs, 33 small nucleolar RNAs, one antisense RNA, and two mRNAs were upregulated, while 37 mRNAs, one tRNA, and 35 antisense RNAs were downregulated. We also confirmed that miRNA211 and miR92a-3p were upregulated, while the expression levels of hypoxia-inducible factor, rat cyclin-dependent kinase 2, and rat platelet-derived growth factor C were reduced in exosomes derived from cAMP-induced differentiated Schwann cells. Venn diagrams were used to identify overlapping miRNA targets from highly expressed miRNAs (miR211-5p, miR211-3p, and miR92a-3p). The pathways identified via Kyoto Encyclopedia of Genes and Genomes analysis of the target genes are associated with nerve regeneration and Schwann cell proliferation such as the tumor necrosis factor signaling pathway, dopaminergic synapse, and neurotrophin signaling, and cAMP-dependent signaling pathways. Additionally, we observed that exosomes derived from differentiated Schwann cells suppressed Schwann cell migration, while control exosomes obtained from undifferentiated Schwann cells did not. Together, the results suggested that exosomes released from differentiated Schwann cells regulated Schwann cell migration through changes in miRNA expression.
- Published
- 2020
17. Localized Hypertrophic Neuropathy as a Neoplastic Manifestation of KRAS-Mediated RASopathy
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Fausto J. Rodriguez, Shivani Ahlawat, Allan J. Belzberg, M. Adelita Vizcaino, Verena Staedtke, Sarra M Belakhoua, and Liam Chen
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Male ,MAPK/ERK pathway ,Pathology ,medicine.medical_specialty ,Schwann cell ,RASopathy ,medicine.disease_cause ,Pathology and Forensic Medicine ,Schwann cell proliferation ,Proto-Oncogene Proteins p21(ras) ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Germline mutation ,Café au lait spot ,Humans ,Medicine ,Child ,030304 developmental biology ,0303 health sciences ,Nerve biopsy ,medicine.diagnostic_test ,business.industry ,Brief Report ,Peripheral Nervous System Diseases ,Hypertrophy ,General Medicine ,medicine.disease ,medicine.anatomical_structure ,Neurology ,Mutation ,Schwann Cells ,Neurology (clinical) ,KRAS ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Localized hypertrophic neuropathy is a rare Schwann cell proliferation that usually affects single nerves from the extremities, and it is of unclear etiology in its pure form. RASopathies are a defined group of genetic diseases with overlapping clinical features, usually secondary to germline mutations in genes encoding either components or regulators of the RAS/MAPK pathway. Herein, we report an 11-year-old boy presenting with café au lait spots and right leg length discrepancy. A fascicular nerve biopsy of the tibial nerve demonstrated a Schwann cell proliferation with prominent onion-bulb formation, satisfying criteria for localized hypertrophic neuropathy. Molecular genetic analysis demonstrated identical KRAS mutations (c38_40dupGCG) in the peripheral nerve lesion and melanocytes from café au lait spots, but not in blood, supporting a diagnosis of a KRAS-mediated rasopathy with mosaicism. Immunohistochemical staining in the peripheral nerve lesion demonstrated strong pERK staining consistent with downstream MAPK pathway activation. This report suggests that at least a subset of localized hypertrophic neuropathies are bonafide, well-differentiated Schwann cell neoplasms developing through oncogenic RAS signaling, which provides new insights into the controversial entity historically known as localized hypertrophic neuropathy.
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- 2020
18. Lithium promotes proliferation and suppresses migration of Schwann cells
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Xiao-Kun Gu, Mei-Ling Lu, Xin-Rui Li, and Hui Xu
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0301 basic medicine ,proliferation ,Schwann cell ,migration ,lcsh:RC346-429 ,Schwann cell proliferation ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Developmental Neuroscience ,5-Ethynyl-2'-deoxyuridine ,medicine ,Viability assay ,Remyelination ,5-ethynyl-2′-deoxyuridine ,cell counting kit-8 ,cell viability ,lithium ,peripheral nerve ,regeneration ,schwann cell ,wound healing assay ,lcsh:Neurology. Diseases of the nervous system ,Migration Assay ,Regeneration (biology) ,Cell Counting Kit-8 ,5-ethynyl-2'-deoxyuridine ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,nervous system ,Wound healing ,030217 neurology & neurosurgery ,Research Article - Abstract
Schwann cell proliferation, migration and remyelination of regenerating axons contribute to regeneration after peripheral nervous system injury. Lithium promotes remyelination by Schwann cells and improves peripheral nerve regeneration. However, whether lithium modulates other phenotypes of Schwann cells, especially their proliferation and migration remains elusive. In the current study, primary Schwann cells from rat sciatic nerve stumps were cultured and exposed to 0, 5, 10, 15, or 30 mM lithium chloride (LiCl) for 24 hours. The effects of LiCl on Schwann cell proliferation and migration were examined using the Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, Transwell and wound healing assays. Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays showed that 5, 10, 15, and 30 mM LiCl significantly increased the viability and proliferation rate of Schwann cells. Transwell-based migration assays and wound healing assays showed that 10, 15, and 30 mM LiCl suppressed the migratory ability of Schwann cells. Furthermore, the effects of LiCl on the proliferation and migration phenotypes of Schwann cells were mostly dose-dependent. These data indicate that lithium treatment significantly promotes the proliferation and inhibits the migratory ability of Schwann cells. This conclusion will inform strategies to promote the repair and regeneration of peripheral nerves. All of the animal experiments in this study were ethically approved by the Administration Committee of Experimental Animal Center of Nantong University, China (approval No. 20170320-017) on March 2, 2017.
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- 2020
19. Conductive conduit small gap tubulization for peripheral nerve repair
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Qicheng Li, Wei Zhang, Feng Rao, Haichang Guo, Baoguo Jiang, Fei Yu, Xingxing Fang, Peixun Zhang, Jiuxu Deng, and Shu-Lin Bai
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Chemistry ,General Chemical Engineering ,Regeneration (biology) ,Motor nerve ,02 engineering and technology ,General Chemistry ,021001 nanoscience & nanotechnology ,Functional recovery ,Schwann cell proliferation ,03 medical and health sciences ,surgical procedures, operative ,0302 clinical medicine ,Electrical conduit ,Peripheral nerve ,Peripheral nerve injury ,Sciatic nerve ,0210 nano-technology ,030217 neurology & neurosurgery ,Biomedical engineering - Abstract
Despite advances in surgical techniques, functional recovery following epineurial neurorrhaphy of transected peripheral nerves often remains quite unsatisfactory. Small gap tubulisation is a promising approach that has shown potential to traditional epineurial neurorrhaphy in the treatment of peripheral nerve injury. Thus, the goal of this study is to evaluate sciatic nerve regeneration after nerve transection, followed by small gap tubulization using a reduced graphene oxide-based conductive conduit. In vitro, the electrically conductive conduit could promote Schwann cell proliferation through PI3K/Akt signaling pathway activation. In vivo, the results of electrophysiological and walking track analysis suggest that the electrically conductive conduit could promote sensory and motor nerve regeneration and functional recovery, which is based on the mechanisms of selective regeneration and multiple-bud regeneration. These promising results illustrate electrically conductive conduit small gap tubulization as an alternative approach for transected peripheral nerve repair.
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- 2020
20. A Procedure for Isolating Schwann Cells Developed for Analysis of the Mouse Embryonic Lethal Mutation NF1
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Kim, Haesun A., Ratner, Nancy, Fedoroff, Sergey, editor, Burkholder, Gary D., editor, Juurlink, Bernhard H. J., editor, Devon, Richard M., editor, Doucette, J. Ronald, editor, Nazarali, Adil J., editor, Schreyer, David J., editor, and Verge, Valerie M. K., editor
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- 1997
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21. Regulation of Connexin Expression in Schwann Cells
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Chandross, Karen J., Spray, David C., Kessler, John A., Spray, David C., and Dermietzel, Rolf
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- 1996
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22. Schwann Cells in Phylogeny
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Stewart, Helen J. S., Jessen, Kristjan R., Vernadakis, Antonia, editor, and Roots, Betty I., editor
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- 1995
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23. Retrovirus-Mediated Gene Transfer of PMP22 in Schwann Cells: Studies on Cell Growth
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Zoidl, Georg, Schmalenbach, Corinne, Müller, Hans Werner, and Salvati, S., editor
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- 1994
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24. Human Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote the Proliferation of Schwann Cells by Regulating the PI3K/AKT Signaling Pathway via Transferring miR-21
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Liming Tang, Dan Zhou, Huanyan Zhang, Jianhua Su, Yongbin Ma, and Fen Qian
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Article Subject ,Chemistry ,Akt/PKB signaling pathway ,Regeneration (biology) ,Mesenchymal stem cell ,Cell Biology ,Regenerative medicine ,RC31-1245 ,Schwann cell proliferation ,Cell biology ,Peripheral nerve injury ,Sciatic nerve ,Molecular Biology ,Internal medicine ,PI3K/AKT/mTOR pathway ,Research Article - Abstract
As an alternative mesenchymal stem cell- (MSC-) based therapy, MSC-derived extracellular vesicles (EVs) have shown promise in the field of regenerative medicine. We previously found that human umbilical cord mesenchymal stem cell-derived EVs (hUCMSC-EVs) improved functional recovery and nerve regeneration in a rat model of sciatic nerve transection. However, the underlying mechanisms are poorly understood. Here, we demonstrated for the first time that hUCMSC-EVs promoted the proliferation of Schwann cells by activating the PI3K/AKT signaling pathway. Furthermore, we showed that hUCMSC-EVs mediated Schwann cell proliferation via transfer of miR-21. Our findings highlight a novel mechanism of hUCMSC-EVs in treating peripheral nerve injury and suggest that hUCMSC-EVs may be an attractive option for clinical application in the treatment of peripheral nerve injury.
- Published
- 2021
25. Evaluation and Comparison of the Effects of Mature Silkworm ( Bombyx mori ) and Silkworm Pupae Extracts on Schwann Cell Proliferation and Axon Growth: An In Vitro Study.
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Khosropanah MH, Majidi Zolbin M, Kajbafzadeh AM, Amani L, Harririan I, Azimzadeh A, Nejatian T, Alizadeh Vaghsloo M, and Hassannejad Z
- Abstract
Background: Silkworm products were first used by physicians more than 8500 years ago, in the early Neolithic period. In Persian medicine, silkworm extract has several uses for treating and preventing neurological, cardiac, and liver diseases. Mature silkworms ( Bombyx mori ) and their pupae contain a variety of growth factors and proteins that can be used in many repair processes, including nerve regeneration., Objectives: The study aimed to evaluate the effects of mature silkworm ( Bombyx mori ), and silkworm pupae extract on Schwann cell proliferation and axon growth., Methods: Silkworm ( Bombyx mori ) and silkworm pupae extracts were prepared. Then, the concentration and type of amino acids and proteins in the extracts were evaluated by Bradford assay, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and liquid chromatograph-mass spectrometer (LC-MS/MS). Also, the regenerative potential of extracts for improving Schwann cell proliferation and axon growth was examined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay, electron microscopy, and NeuroFilament-200 (NF-200) immunostaining., Results: According to the results of the Bradford test, the total protein content of pupae extract was almost twice that of mature worm extract. Also, SDS-PAGE analysis revealed numerous proteins and growth factors, such as bombyrin and laminin, in extracts that are involved in the repair of the nervous system. In accordance with Bradford's results, the evaluation of extracts using LC-MS/MS revealed that the number of amino acids in pupae extract was higher than in mature silkworm extract. It was found that the proliferation of Schwann cells at a concentration of 0.25 mg/mL in both extracts was higher than the concentrations of 0.01 and 0.05 mg/mL. When using both extracts on dorsal root ganglion (DRGs), an increase in length and number was observed in axons., Conclusions: The findings of this study demonstrated that extracts obtained from silkworms, especially pupae, can play an effective role in Schwann cell proliferation and axonal growth, which can be strong evidence for nerve regeneration, and, consequently, repairing peripheral nerve damage., Competing Interests: Conflict of Interests: The authors declared no conflict of interests., (Copyright © 2023, Author(s).)
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- 2023
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26. The Growing Biological Scenario of Growth Arrest
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Schneider, C., Del Sal, G., Brancolini, C., Gustincich, S., Manfioletti, G., Ruaro, M. E., Fanning, Ellen, editor, Knippers, Rolf, editor, and Winnacker, Ernst-L., editor
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- 1993
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27. Transcriptional regulation of miR-30a by YAP impacts PTPN13 and KLF9 levels and Schwann cell proliferation
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Sany Hoxha, David Harbaugh, Scott Troutman, Michael S. Kareta, Joseph L. Kissil, and Alyssa Shepard
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TEAD, TEA domain ,TFs, transcription factors ,YAP, yes-associated protein ,Transcription, Genetic ,Hippo pathway ,AKT, protein kinase B ,Regulator ,Kruppel-Like Transcription Factors ,Protein Tyrosine Phosphatase, Non-Receptor Type 13 ,Down-Regulation ,Biology ,Biochemistry ,Schwann cell proliferation ,KLF9, Kruppel like factor 9 ,Cell Line, Tumor ,IRS-1, insulin receptor substrate ,Transcriptional regulation ,transcription coactivator ,Humans ,Schwann cells ,Molecular Biology ,Transcription factor ,PI3K/AKT/mTOR pathway ,miRNA ,Adaptor Proteins, Signal Transducing ,Cell Proliferation ,Hippo signaling pathway ,PTPN13, protein tyrosine phosphatase non-receptor type 13 ,Cell Differentiation ,YAP-Signaling Proteins ,Cell Biology ,yes-associated protein (YAP) ,KD, knock-down ,Cell biology ,KLF9 ,MicroRNAs ,PI3K, phosphoinositide 3-kinases ,Regulatory Pathway ,qPCR, quantitative PCR ,ChIP-seq, chromatin immunoprecipitation sequencing ,hSC2λ, human Schwann ,Research Article ,Signal Transduction - Abstract
The Hippo pathway is a key regulatory pathway that is tightly regulated by mechanical cues such as tension, pressure, and contact with the extracellular matrix and other cells. At the distal end of the pathway is the yes-associated protein (YAP), a well-characterized transcriptional regulator. Through binding to transcription factors such as the TEA Domain TFs (TEADs) YAP regulates expression of several genes involved in cell fate, proliferation and death decisions. While the function of YAP as direct transcriptional regulator has been extensively characterized, only a small number of studies examined YAP function as a regulator of gene expression via microRNAs. We utilized bioinformatic approaches, including chromatin immunoprecipitation sequencing and RNA-Seq, to identify potential new targets of YAP regulation and identified miR-30a as a YAP target gene in Schwann cells. We find that YAP binds to the promoter and regulates the expression of miR-30a. Moreover, we identify several YAP-regulated genes that are putative miR-30a targets and focus on two of these, protein tyrosine pohosphatase non-receptor type 13 (PTPN13) and Kruppel like factor 9. We find that YAP regulation of Schwann cell proliferation and death is mediated, to a significant extent, through miR-30a regulation of PTPN13 in Schwann cells. These findings identify a new regulatory function by YAP, mediated by miR-30a, to downregulate expression of PTPN13 and Kruppel like factor 9. These studies expand our understanding of YAP function as a regulator of miRNAs and illustrate the complexity of YAP transcriptional functions.
- Published
- 2021
28. H3K27 demethylases are dispensable for activation of Polycomb-regulated injury response genes in peripheral nerve
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Ki H. Ma, Raghu Ramesh, Seongsik Won, Phu Duong, John Svaren, and John J. Moran
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0301 basic medicine ,Schwann ,Jumonji Domain-Containing Histone Demethylases ,injury ,Schwann cell ,histone ,nerve ,Biology ,demethylase ,Biochemistry ,Methylation ,Schwann cell proliferation ,Histones ,03 medical and health sciences ,Mice ,Peripheral Nerve Injuries ,medicine ,SUZ12 ,Animals ,Humans ,Molecular Biology ,Gene knockout ,Cyclin-Dependent Kinase Inhibitor p16 ,Histone Demethylases ,030102 biochemistry & molecular biology ,fungi ,Polycomb Repressive Complex 2 ,Ubiquitination ,Gene Expression Regulation, Developmental ,Cell Biology ,Nerve injury ,Cell biology ,Polycomb ,Histone Code ,030104 developmental biology ,medicine.anatomical_structure ,Histone ,SUZ12, suppressor of zeste 12 ,biology.protein ,Demethylase ,Schwann Cells ,medicine.symptom ,PRC, Polycomb repressive complex ,PRC2 ,Research Article - Abstract
The induction of nerve injury response genes in Schwann cells depends on both transcriptional and epigenomic reprogramming. The nerve injury response program is regulated by the repressive histone mark H3K27 trimethylation (H3K27me3), deposited by Polycomb repressive complex 2 (PRC2). Loss of PRC2 function leads to early and augmented induction of the injury response gene network in peripheral nerves, suggesting H3K27 demethylases are required for derepression of Polycomb-regulated nerve injury genes. To determine the function of H3K27 demethylases in nerve injury, we generated Schwann cell–specific knockouts of H3K27 demethylase Kdm6b and double knockouts of Kdm6b/Kdm6a (encoding JMJD3 and UTX). We found that H3K27 demethylases are largely dispensable for Schwann cell development and myelination. In testing the function of H3K27 demethylases after injury, we found early induction of some nerve injury genes was diminished compared with control, but most injury genes were largely unaffected at 1 and 7 days post injury. Although it was proposed that H3K27 demethylases are required to activate expression of the cyclin-dependent kinase inhibitor Cdkn2a in response to injury, Schwann cell–specific deletion of H3K27 demethylases affected neither the expression of this gene nor Schwann cell proliferation after nerve injury. To further characterize the regulation of nerve injury response genes, we found that injury genes are associated with repressive histone H2AK119 ubiquitination catalyzed by PRC1, which declines after injury. Overall, our results indicate H3K27 demethylation is not required for induction of injury response genes and that other mechanisms likely are involved in activating Polycomb-repressed injury genes in peripheral nerve.
- Published
- 2021
29. RABL6A Regulates Schwann Cell Senescence in an RB1-Dependent Manner
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Aloysius J. Klingelhutz, Shaikamjad Umesalma, Jordan L. Kohlmeyer, Francoise A. Gourronc, Courtney A. Kaemmer, and Dawn E. Quelle
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Senescence ,senescence ,QH301-705.5 ,Carcinogenesis ,Ubiquitin-Protein Ligases ,Schwann cell ,Endogeny ,Biology ,Article ,Catalysis ,Schwann cell proliferation ,Malignant transformation ,law.invention ,Inorganic Chemistry ,retinoblastoma protein (RB1) ,MPNST ,law ,medicine ,Humans ,Gene silencing ,Biology (General) ,Physical and Theoretical Chemistry ,QD1-999 ,Molecular Biology ,Cells, Cultured ,Cellular Senescence ,Spectroscopy ,Cell Proliferation ,Oncogene Proteins ,Neurofibroma ,Cell Cycle ,Organic Chemistry ,General Medicine ,Cell cycle ,Computer Science Applications ,Cell biology ,Chemistry ,Retinoblastoma Binding Proteins ,Cell Transformation, Neoplastic ,HEK293 Cells ,medicine.anatomical_structure ,Neurofibrosarcoma ,rab GTP-Binding Proteins ,Suppressor ,Schwann Cells ,RABL6A - Abstract
Schwann cells are normally quiescent, myelinating glia cells of the peripheral nervous system. Their aberrant proliferation and transformation underlie the development of benign tumors (neurofibromas) as well as deadly malignant peripheral nerve sheath tumors (MPNSTs). We discovered a new driver of MPNSTs, an oncogenic GTPase named RABL6A, that functions in part by inhibiting the RB1 tumor suppressor. RB1 is a key mediator of cellular senescence, a permanent withdrawal from the cell cycle that protects against cell immortalization and transformation. Based on the RABL6A-RB1 link in MPNSTs, we explored the hypothesis that RABL6A promotes Schwann cell proliferation and abrogates their senescence by inhibiting RB1. Using sequentially passaged normal human Schwann cells (NHSCs), we found that the induction of replicative senescence was associated with reduced expression of endogenous RABL6A. Silencing RABL6A in low passage NHSCs caused premature stress-induced senescence, which was largely rescued by co-depletion of RB1. Consistent with those findings, Rabl6-deficient MEFs displayed impaired proliferation and accelerated senescence compared to wildtype MEFs. These results demonstrate that RABL6A is required for maintenance of proper Schwann cell proliferation and imply that aberrantly high RABL6A expression may facilitate malignant transformation.
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- 2021
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30. A Subpopulation of Schwann Cell-Like Cells With Nerve Regeneration Signatures Is Identified Through Single-Cell RNA Sequencing
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Shijie Tang, Sitian Xie, Shenyou Shu, Kaiyu Nie, Mingjun Zhang, Zairong Wei, and Haihong Li
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NRG1 ,Physiology ,Regeneration (biology) ,Cell ,Mesenchymal stem cell ,Schwann cell-like cells ,Schwann cell ,Biology ,single-cell RNA sequencing ,Schwann cell proliferation ,Cell biology ,Vascular endothelial growth factor A ,medicine.anatomical_structure ,stem cells ,Physiology (medical) ,medicine ,QP1-981 ,Stem cell ,nerve regeneration ,Gene ,Original Research - Abstract
Schwann cell-like cells (SCLCs) derived from human amniotic mesenchymal stem cells (hAMSCs) have been shown to promote peripheral nerve regeneration, but the underlying molecular mechanism was still poorly understood. In order to investigate the heterogeneity and potential molecular mechanism of SCLCs in the treatment of peripheral nerve regeneration at a single cell level, single-cell RNA sequencing was applied to profile single cell populations of hAMSCs and SCLCs. We profiled 6,008 and 5,140 single cells from hAMSCs and SCLCs, respectively. Based on bioinformatics analysis, pathways associated with proliferation, ECM organization, and tissue repair were enriched within both populations. Cell cycle analysis indicated that single cells within these two populations remained mostly in the G0/G1 phase. The transformation of single cells from hAMSCs to SCLCs was characterized by pseudotime analysis. Furthermore, we identified a subpopulation of SCLCs that highly expressed genes associated with Schwann cell proliferation, migration, and survival, such as JUN, JUND, and NRG1., Genes such as PTGS2, PITX1, VEGFA, and FGF2 that promote nerve regeneration were also highly expressed in single cells within this subpopulation, and terms associated with inflammatory and tissue repair were enriched in this subpopulation by pathway enrichment analysis. Our results indicate that a subpopulation of SCLCs with nerve regeneration signatures may be the key populations that promote nerve regeneration.
- Published
- 2021
31. Growth Factors in Human Glial Cells in Culture
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Kim, S. U., Yong, V. W., Jeserich, Gunnar, editor, Althaus, Hans H., editor, and Waehneldt, Thomas V., editor
- Published
- 1990
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32. Dysregulated Transcription Factor TFAP2A After Peripheral Nerve Injury Modulated Schwann Cell Phenotype
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Sheng Yi, Hui Xu, Xiaokun Gu, and Fuchao Zhang
- Subjects
Male ,0301 basic medicine ,Schwann cell ,Biology ,Biochemistry ,Schwann cell proliferation ,Rats, Sprague-Dawley ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Cell Movement ,Peripheral Nerve Injuries ,medicine ,Animals ,Transcription factor ,Cell Proliferation ,General Medicine ,Sciatic nerve injury ,Nerve injury ,medicine.disease ,Sciatic Nerve ,Up-Regulation ,Cell biology ,Phenotype ,030104 developmental biology ,medicine.anatomical_structure ,Transcription Factor AP-2 ,Peripheral nerve injury ,Schwann Cells ,IRF8 ,medicine.symptom ,Transcription Factor Gene ,030217 neurology & neurosurgery - Abstract
Transcription factors regulate the transcriptions and expressions of numerous target genes and direct a variety of physiological and pathological activities. To obtain a better understanding of the involvement of transcription factors during peripheral nerve repair and regeneration, significantly differentially expressed genes coding for transcription factors in rat sciatic nerves after sciatic nerve crush injury were identified. A total of 9 transcription factor genes, including GBX2, HIF3A, IRF8, LRRC63, SNAI3, SPIB, TBX21, TFAP2A, and ZBTB16 were identified to be commonly differentially expressed at 1, 4, 7, and 14 days after nerve injury. TFAP2A, a gene encoding transcription factor activating enhancer binding protein 2 alpha, was found to be critical in the regulatory network. PCR validation and immunohistochemistry staining of injured rat sciatic nerves showed that TFAP2A expression was significantly up-regulated in the Schwann cells after nerve injury for at least 2 weeks. Schwann cells transfected with TFAP2A-siRNA exhibited elevated proliferation rate and migration ability, suggesting that TFAP2A suppressed Schwann cell proliferation and migration. Collectively, our study provided a global overview of the dynamic changes of transcription factors after sciatic nerve injury, discovered key transcription factors for the regeneration process, and deepened the understanding of the molecular mechanisms underlying peripheral nerve repair and regeneration.
- Published
- 2019
33. A Schwann cell–enriched circular RNA circ‐Ankib1 regulates Schwann cell proliferation following peripheral nerve injury
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Shuoshuo Zhou, Wei Feng, Tao Huang, Gu Xiaosong, Susu Mao, Bin Yu, and Shanshan Zhang
- Subjects
0301 basic medicine ,Nervous system ,Schwann cell ,Biology ,Biochemistry ,Schwann cell proliferation ,DEAD-box RNA Helicases ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,Peripheral Nerve Injuries ,Genetics ,medicine ,Animals ,Axon ,Molecular Biology ,Cell Proliferation ,Research ,RNA, Circular ,Retinoic Acid 4-Hydroxylase ,Sciatic nerve injury ,Nerve injury ,medicine.disease ,Nerve Regeneration ,Rats ,Cell biology ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,Peripheral nerve injury ,Female ,Schwann Cells ,Sciatic nerve ,medicine.symptom ,030217 neurology & neurosurgery ,Biotechnology - Abstract
Schwann cells (SCs) play an essential role in nerve injury repair. A striking feature of the cellular response to peripheral nerve injury is the proliferation of SCs. Circular (circ)RNAs are enriched in the nervous system and are involved in physiologic and pathologic processes. However, the potential role of circRNAs in SC proliferation post nerve injury remains largely unknown. Using a sciatic nerve crush model, we obtained an expression profiling of circRNAs in injured sciatic nerves in rats by RNA sequencing and bioinformatics analysis, and we further identified a circRNA [circ–ankyrin repeat and in-between Ring finger (IBR) domain containing 1 (Ankib1)] involved in SC proliferation by the transfection of specific small interfering RNAs. Overexpression of circ-Ankib1, which was specifically and highly enriched in SCs, impaired SC proliferation and axon regeneration following sciatic nerve injury. Mechanistically, increased expression of DEx/H-box helicase 9 (DHX9) postinjury might contribute to the down-regulation of circ-Ankib1, which further suppressed cytochrome P450, family 26, subfamily B, polypeptide 1 expression by sponging miR-423-5p, miR-485-5p, and miR-666-3p, leading to the induction of SC proliferation and nerve regeneration. Taken together, our results reveal a crucial role for circRNAs in regulating proliferation of SCs involved in sciatic nerve regeneration; as such, circRNAs may serve as a potential therapeutic avenue for nerve injury repair.—Mao, S., Zhang, S., Zhou, S., Huang, T., Feng, W., Gu, X., Yu, B. A Schwann cell–enriched circular RNA circ-Ankib1 regulates Schwann cell proliferation following peripheral nerve injury.
- Published
- 2019
34. Optogenetic stimulation promotes Schwann cell proliferation, differentiation, and myelination in vitro
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Sujin Hyung, Sung Rae Cho, Noo Li Jeon, Kyu-Hwan Jung, Sung-Yon Kim, and Jihye Park
- Subjects
0301 basic medicine ,Nervous system ,Light ,lcsh:Medicine ,Stimulation ,Inositol 1,4,5-Trisphosphate ,Article ,Schwann cell proliferation ,Calcium Channels, T-Type ,Mice ,03 medical and health sciences ,Myelin ,0302 clinical medicine ,medicine ,Animals ,lcsh:Science ,Cells, Cultured ,Early Growth Response Protein 2 ,Cell Proliferation ,Motor Neurons ,Multidisciplinary ,biology ,Chemistry ,Calcium channel ,lcsh:R ,Cell Differentiation ,Myelin Basic Protein ,Coculture Techniques ,Culture Media ,Myelin basic protein ,Cell biology ,Optogenetics ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,biology.protein ,Calcium ,lcsh:Q ,Schwann Cells ,Neuron ,030217 neurology & neurosurgery ,Intracellular - Abstract
Schwann cells (SCs) constitute a crucial element of the peripheral nervous system, by structurally supporting the formation of myelin and conveying vital trophic factors to the nervous system. However, the functions of SCs in developmental and regenerative stages remain unclear. Here, we investigated how optogenetic stimulation (OS) of SCs regulates their development. In SC monoculture, OS substantially enhanced SC proliferation and the number of BrdU+-S100ß+-SCs over time. In addition, OS also markedly promoted the expression of both Krox20 and myelin basic protein (MBP) in SC culture medium containing dBcAMP/NRG1, which induced differentiation. We found that the effects of OS are dependent on the intracellular Ca2+ level. OS induces elevated intracellular Ca2+ levels through the T-type voltage-gated calcium channel (VGCC) and mobilization of Ca2+ from both inositol 1,4,5-trisphosphate (IP3)-sensitive stores and caffeine/ryanodine-sensitive stores. Furthermore, we confirmed that OS significantly increased expression levels of both Krox20 and MBP in SC-motor neuron (MN) coculture, which was notably prevented by pharmacological intervention with Ca2+. Taken together, our results demonstrate that OS of SCs increases the intracellular Ca2+ level and can regulate proliferation, differentiation, and myelination, suggesting that OS of SCs may offer a new approach to the treatment of neurodegenerative disorders.
- Published
- 2019
35. Asymmetrical 3D Nanoceria Channel for Severe Neurological Defect Regeneration
- Author
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Hui Li, Cunyi Fan, Qixin Han, Weien Yuan, Yun Qian, and Xiaotian Zhao
- Subjects
0301 basic medicine ,Angiogenesis ,Nerve guidance conduit ,Neurosurgery ,02 engineering and technology ,macromolecular substances ,medicine.disease_cause ,Article ,Schwann cell proliferation ,Biomaterials ,03 medical and health sciences ,medicine ,Nanotechnology ,lcsh:Science ,Microvessel ,Multidisciplinary ,Chemistry ,Regeneration (biology) ,021001 nanoscience & nanotechnology ,Cell biology ,030104 developmental biology ,Peripheral nerve injury ,lcsh:Q ,Sciatic nerve ,0210 nano-technology ,Oxidative stress - Abstract
Summary Inflammation and oxidative stress are major problems in peripheral nerve injury. Nanoceria can manipulate antioxidant factor expression, stimulate angiogenesis, and assist in axonal regeneration. We fabricate collagen/nanoceria/polycaprolactone (COL/NC/PCL) conduit by asymmetrical three-dimensional manufacture and find that this scaffold successfully improves Schwann cell proliferation, adhesion, and neural expression. In a 15-mm rat sciatic nerve defect model, we further confirm that the COL/NC/PCL conduit markedly alleviates inflammation and oxidative stress, improves microvessel growth, and contributes to functional, electrophysiological, and morphological nerve restoration in the long term. Our findings provide compelling evidence for future research in antioxidant nerve conduit for severe neurological defects., Graphical Abstract, Highlights • Collagen/nanoceria/polycaprolactone conduit was prepared by asymmetrical fabrication • The scaffold induced proliferation, adhesion, and angiogenesis in nerve repair • The scaffold alleviated oxidative stress and inflammation in the microenvironment, Biomaterials; Nanotechnology; Neurosurgery
- Published
- 2019
36. Increased levels of miR-3099 induced by peripheral nerve injury promote Schwann cell proliferation and migration
- Author
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Zhang-Chun Cheng, Yang Miao, Qianyan Liu, Tianmei Qian, Pan Wang, and Xinghui Wang
- Subjects
0301 basic medicine ,miR-3099 ,proliferation ,sciatic nerve ,Biology ,migration ,lcsh:RC346-429 ,Schwann cell proliferation ,03 medical and health sciences ,0302 clinical medicine ,Developmental Neuroscience ,nerve regeneration ,peripheral nerve injury ,gene expression ,Schwann cells ,target genes ,mechanisms ,neural regeneration ,Gene expression ,microRNA ,medicine ,Gene ,lcsh:Neurology. Diseases of the nervous system ,Sciatic nerve injury ,medicine.disease ,Phenotype ,Cell biology ,030104 developmental biology ,nervous system ,Peripheral nerve injury ,Sciatic nerve ,030217 neurology & neurosurgery ,Research Article - Abstract
MicroRNAs (miRNAs) can regulate the modulation of the phenotype of Schwann cells. Numerous novel miRNAs have been discovered and identified in rat sciatic nerve segments, including miR-3099. In the current study, miR-3099 expression levels following peripheral nerve injury were measured in the proximal stumps of rat sciatic nerves after surgical crush. Real-time reverse transcription-polymerase chain reaction was used to determine miR-3099 expression in the crushed nerve segment at 0, 1, 4, 7, and 14 days post sciatic nerve injury, which was consistent with Solexa sequencing outcomes. Expression of miR-3099 was up-regulated following peripheral nerve injury. EdU and transwell chamber assays were used to observe the effect of miR-3099 on Schwann cell proliferation and migration. The results showed that increased miR-3099 expression promoted the proliferation and migration of Schwann cells. However, reduced miR-3099 expression suppressed the proliferation and migration of Schwann cells. The potential target genes of miR-3099 were also investigated by bioinformatic tools and high-throughput outcomes. miR-3099 targets genes Aqp4, St8sia2, Tnfsf15, and Zbtb16 and affects the proliferation and migration of Schwann cells. This study examined the levels of miR-3099 at different time points following peripheral nerve injury. Our results confirmed that increased miR-3099 level induced by peripheral nerve injury can promote the proliferation and migration of Schwann cells.
- Published
- 2019
37. Folic acid contributes to peripheral nerve injury repair by promoting Schwann cell proliferation, migration, and secretion of nerve growth factor
- Author
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Yong-Jie Chen, Wei-bo Kang, Jia-Zhi Yan, and Du-Yi Lu
- Subjects
0301 basic medicine ,medicine.medical_specialty ,medicine.medical_treatment ,Intraperitoneal injection ,Schwann cell ,lcsh:RC346-429 ,Schwann cell proliferation ,folic acid ,03 medical and health sciences ,0302 clinical medicine ,Developmental Neuroscience ,Internal medicine ,medicine ,peripheral nerve injury ,Axon ,nerve regeneration ,neurotrophic factor ,lcsh:Neurology. Diseases of the nervous system ,cell functions ,peripheral nerve repair ,tissue engineering ,neural regeneration ,biomaterial ,Cell growth ,Chemistry ,Sciatic nerve injury ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Nerve growth factor ,Peripheral nerve injury ,030217 neurology & neurosurgery ,Research Article - Abstract
After peripheral nerve injury, intraperitoneal injection of folic acid improves axon quantity, increases axon density and improves electromyography results. However, the mechanisms for this remain unclear. This study explored whether folic acid promotes peripheral nerve injury repair by affecting Schwann cell function. Primary Schwann cells were obtained from rats by in vitro separation and culture. Cell proliferation, assayed using the Cell Counting Kit-8 assay, was higher in cells cultured for 72 hours with 100 mg/L folic acid compared with the control group. Cell proliferation was also higher in the 50, 100, 150, and 200 mg/L folic acid groups compared with the control group after culture for 96 hours. Proliferation was markedly higher in the 100 mg/L folic acid group compared with the 50 mg/L folic acid group and the 40 ng/L nerve growth factor group. In Transwell assays, the number of migrated Schwann cells dramatically increased after culture with 100 and 150 mg/L folic acid compared with the control group. In nerve growth factor enzyme-linked immunosorbent assays, treatment of Schwann cell cultures with 50, 100, and 150 mg/L folic acid increased levels of nerve growth factor in the culture medium compared with the control group at 3 days. The nerve growth factor concentration of Schwann cell cultures treated with 100 mg/L folic acid group was remarkably higher than that in the 50 and 150 mg/L folic acid groups at 3 days. Nerve growth factor concentration in the 10, 50, and 100 mg/L folic acid groups was higher than that in the control group at 7 days. The nerve growth factor concentration in the 50 mg/L folic acid group was remarkably higher than that in the 10 and 100 mg/L folic acid groups at 7 days. In vivo, 80 μg/kg folic acid was intraperitoneally administrated for 7 consecutive days after sciatic nerve injury. Immunohistochemical staining showed that the number of Schwann cells in the folic acid group was greater than that in the control group. We suggest that folic acid may play a role in improving the repair of peripheral nerve injury by promoting the proliferation and migration of Schwann cells and the secretion of nerve growth factors.
- Published
- 2019
38. Novel miRNA, miR-sc14, promotes Schwann cell proliferation and migration
- Author
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Zhang-Chun Cheng, Xi-Meng Ji, Pan Wang, Xinghui Wang, Tianmei Qian, Xiao-Dong Cai, Qianyan Liu, and Shan-Shan Wang
- Subjects
0301 basic medicine ,cell migration ,nerve regeneration ,novel microRNAs ,miR-sc14 ,peripheral nerve injury ,cell proliferation ,Schwann cells ,fibroblast growth factor receptor 2 ,biological functions ,peripheral nerve regeneration ,regulatory mechanisms ,neural regeneration ,Biology ,lcsh:RC346-429 ,Schwann cell proliferation ,03 medical and health sciences ,0302 clinical medicine ,Developmental Neuroscience ,medicine ,lcsh:Neurology. Diseases of the nervous system ,Fibroblast growth factor receptor 2 ,Regeneration (biology) ,Cell migration ,Nerve injury ,Sciatic nerve injury ,medicine.disease ,Cell biology ,030104 developmental biology ,Peripheral nerve injury ,Sciatic nerve ,medicine.symptom ,030217 neurology & neurosurgery ,Research Article - Abstract
MicroRNAs refer to a class of endogenous, short non-coding RNAs that mediate numerous biological functions. MicroRNAs regulate various physiological and pathological activities of peripheral nerves, including peripheral nerve repair and regeneration. Previously, using a rat sciatic nerve injury model, we identified many functionally annotated novel microRNAs, including miR-sc14. Here, we used real-time reverse transcription-polymerase chain reaction to examine miR-sc14 expression in rat sciatic nerve stumps. Our results show that miR-sc14 is noticeably altered following sciatic nerve injury, being up-regulated at 1 day and diminished at 7 days. EdU and transwell chamber assay results showed that miR-sc14 mimic promoted proliferation and migration of Schwann cells, while miR-sc14 inhibitor suppressed their proliferation and migration. Additionally, bioinformatic analysis examined potential target genes of miR-sc14, and found that fibroblast growth factor receptor 2 might be a potential target gene. Specifically, our results show changes of miR-sc14 expression in the sciatic nerve of rats at different time points after nerve injury. Appropriately, up-regulation of miR-sc14 promoted proliferation and migration of Schwann cells. Consequently, miR-sc14 may be an intervention target to promote repair of peripheral nerve injury. The study was approved by the Jiangsu Provincial Laboratory Animal Management Committee, China on March 4, 2015 (approval No. 20150304-004).
- Published
- 2019
39. STAT3 inhibition reduces macrophage number and tumor growth in neurofibroma
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Nancy Ratner, Edwin Jousma, Mitchell G. Springer, Jianqiang Wu, Jonathan S. Fletcher, Tilat A. Rizvi, Mi-Ok Kim, Kwangmin Choi, and Eva Dombi
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STAT3 Transcription Factor ,0301 basic medicine ,Cancer Research ,Chemokine ,Curcumin ,Neurofibromatosis 1 ,Down-Regulation ,Schwann cell ,Article ,Schwann cell proliferation ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Plexiform neurofibroma ,Genetics ,medicine ,Animals ,Humans ,Neurofibroma ,Macrophage ,Molecular Biology ,CCL12 ,Chemokine CCL2 ,Cell Proliferation ,Neurofibroma, Plexiform ,Cell Death ,biology ,Macrophages ,Janus Kinase 2 ,medicine.disease ,Monocyte Chemoattractant Proteins ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Cytokines ,Schwann Cells ,Macrophage proliferation ,Signal Transduction - Abstract
Plexiform neurofibroma, a benign peripheral nerve tumor, is associated with the biallelic loss of function of the NF1 tumor suppressor in Schwann cells. Here, we show that FLLL32, a small molecule inhibitor of JAK2/STAT3 signaling, reduces neurofibroma growth in mice with conditional, biallelic deletion of Nf1 in the Schwann cell lineage. FLLL32 treatment or Stat3 deletion in tumor cells reduced inflammatory cytokine expression and tumor macrophage numbers in neurofibroma. Although STAT3 inhibition downregulated the chemokines CCL2 and CCL12, which can signal through CCR2 to recruit macrophages to peripheral nerves, deletion of Ccr2 did not improve survival or reduce macrophage numbers in neurofibroma-bearing mice. Interestingly, Iba1+; F4/80+;CD11b+ macrophages accounted for ~20-40% of proliferating cells in untreated tumors. FLLL32 suppressed macrophage proliferation, implicating STAT3-dependent, local proliferation in neurofibroma macrophage accumulation, and decreased Schwann cell proliferation and increased Schwann cell death. The functions of STAT3 signaling in neurofibroma Schwann cells and macrophages, and its relevance as a therapeutic target in neurofibroma, merit further investigation.
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- 2018
40. Cyr61 promotes Schwann cell proliferation and migration via αvβ3 integrin
- Author
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Yuhan Chen, Mi Shen, Yuhua Ji, Zhenghui Cheng, Fei Ding, Yawen Zhang, Yinchao Tian, and Han Wu
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0301 basic medicine ,Male ,Proliferation ,Biology ,Schwann cell proliferation ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,medicine ,Animals ,Schwann cells ,Axon ,lcsh:QH573-671 ,Autocrine signalling ,Molecular Biology ,Cells, Cultured ,Migration ,Cell Proliferation ,integumentary system ,lcsh:Cytology ,Regeneration (biology) ,Cell Biology ,Nerve injury ,Integrin alphaVbeta3 ,In vitro ,Cell biology ,Rats ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,CYR61 ,Peripheral nerve injury ,Cyr61 ,medicine.symptom ,030217 neurology & neurosurgery ,Cysteine-Rich Protein 61 ,Research Article - Abstract
Background Schwann cells (SCs) play a crucial role in the repair of peripheral nerves. This is due to their ability to proliferate, migrate, and provide trophic support to axon regrowth. During peripheral nerve injury, SCs de-differentiate and reprogram to gain the ability to repair nerves. Cysteine-rich 61 (Cyr61/CCN1) is a member of the CCN family of matrix cell proteins and have been reported to be abundant in the secretome of repair mediating SCs. In this study we investigate the function of Cyr61 in SCs. Results We observed Cyr61 was expressed both in vivo and in vitro. The promoting effect of Cyr61 on SC proliferation and migration was through autocrine and paracrine mechanisms. SCs expressed αvβ3 integrin and the effect of Cyr61 on SC proliferation and migration could be blocked via αvβ3 integrin. Cyr61 could influence c-Jun protein expression in cultured SCs. Conclusions In this study, we found that Cyr61 promotes SC proliferation and migration via αvβ3 integrin and regulates c-Jun expression. Our study contributes to the understanding of cellular and molecular mechanisms underlying SC’s function during nerve injury, and thus, may facilitate the regeneration of peripheral nerves after injury.
- Published
- 2021
41. Leukemia inhibitory factor regulates Schwann cell proliferation and migration and affects peripheral nerve regeneration
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Qianqian Chen, Shiying Li, Yunsong Zhang, Qianyan Liu, and Sheng Yi
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Cancer Research ,endocrine system ,Immunology ,Leukemia Inhibitory Factor ,Article ,Schwann cell proliferation ,Cellular and Molecular Neuroscience ,Cell Movement ,medicine ,Animals ,Cell migration ,Axon ,Regeneration and repair in the nervous system ,reproductive and urinary physiology ,Cell Proliferation ,QH573-671 ,Chemistry ,Schwann cell migration ,Cell Biology ,Nerve injury ,Sciatic nerve injury ,medicine.disease ,Cell biology ,Nerve Regeneration ,Rats ,medicine.anatomical_structure ,nervous system ,Peripheral nerve injury ,embryonic structures ,Schwann Cells ,medicine.symptom ,Cytology ,Leukemia inhibitory factor ,hormones, hormone substitutes, and hormone antagonists - Abstract
Leukemia inhibitory factor (LIF) is a pleiotropic cytokine that stimulates neuronal development and survival. Our previous study has demonstrated that LIF mRNA is dysregulated in the peripheral nerve segments after nerve injury. Here, we show that LIF protein is abundantly expressed in Schwann cells after rat sciatic nerve injury. Functionally, suppressed or elevated LIF increases or decreases the proliferation rate and migration ability of Schwann cells, respectively. Morphological observations demonstrate that in vivo application of siRNA against LIF after peripheral nerve injury promotes Schwann cell migration and proliferation, axon elongation, and myelin formation. Electrophysiological and behavior assessments disclose that knockdown of LIF benefits the function recovery of injured peripheral nerves. Differentially expressed LIF affects the metabolism of Schwann cells and negatively regulates ERFE (Erythroferrone). Collectively, our observations reveal the essential roles for LIF in regulating the proliferation and migration of Schwann cells and the regeneration of injured peripheral nerves, discover ERFE as a downstream effector of LIF, and extend our understanding of the molecular mechanisms underlying peripheral nerve regeneration.
- Published
- 2021
42. A novel effect of ethyl pyruvate in Schwann cell de-differentiation and proliferation during Wallerian degeneration.
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Park, Byung Sun, Jo, Hyun Woo, Park, Chan, Huh, Youngbuhm, Jung, Junyang, and Jeong, Na Young
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- *
PYRUVATES , *SCHWANN cells , *CELL differentiation , *OXIDATIVE stress , *NEURODEGENERATION - Abstract
Ethyl pyruvate (EP), as a pyruvate derivative, has the protective effect on oxidative-stress-mediated cellular injury. In previous studies, it has been reported that EP provides protection against neuronal injury in brain, for example transient cerebral ischemia. However, the inhibition effect of EP on peripheral nerve injury is still unknown. Here, we investigated the inhibition effect of EP in Schwann cell de-differentiation and proliferation during Wallerian degeneration using ex vivo sciatic nerve explant system. We demonstrated that EP inhibits p-ERK1/2, p75NGFR, and lysosomal associated membrane protein 1 as factors implicated in Schwann cell de-differentiation during Wallerian degeneration. In addition, EP is sufficient to inhibit Schwann cell proliferation during Wallerian degeneration. Together, these findings suggest that EP has a strong protective effect on Wallerain degeneration. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
43. Sericin Nerve Guidance Conduit Delivering Therapeutically Repurposed Clobetasol for Functional and Structural Regeneration of Transected Peripheral Nerves
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Zheng Wang, Hui Wang, Guobin Wang, Lei Zhang, Xiaolin Li, Jian Wang, Yu Song, Qiangfei Su, Lin Wang, Wen Yang, and Hongjian Xie
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business.industry ,Regeneration (biology) ,0206 medical engineering ,Biomedical Engineering ,Nerve guidance conduit ,02 engineering and technology ,Pharmacology ,021001 nanoscience & nanotechnology ,020601 biomedical engineering ,Sericin ,Nerve conduction velocity ,Schwann cell proliferation ,Biomaterials ,Neurotrophic factors ,Peripheral nerve injury ,Medicine ,Sciatic nerve ,0210 nano-technology ,business - Abstract
Peripheral nerve injury often causes significant function loss. Autologous nerve grafting as a gold-standard repair strategy for treating such an injury is limited by donor nerve supply. Tissue-engineered nerve guidance conduits (TENGCs) as a promising alternative for autografting are challenged by large nerve gaps. Herein, we fabricate a glutaraldehyde-cross-linked sericin nerve guidance conduit (GSC) incorporated with clobetasol, a glucocorticoid receptor agonist, for repairing a 10 mm long sciatic nerve gap in a rat model. The GSC exhibits biocompatibility and regeneration-favorable physicochemical properties. GSC's degradation products promote the secretion of neurotrophic factors in Schwann cells. By repurposing clobetasol for peripheral nerve regeneration, our work uncovers clobetasol's previously unknown functions in promoting Schwann cell proliferation and upregulating the expression of myelin-related genes. Importantly, the implantation of this clobetasol-loaded GSC in vivo leads to successful regeneration of the transected sciatic nerve. Strikingly, the regeneration outcome is functionally comparable to that of autologous nerve grafting (evidenced by three parameters). Specifically, the static sciatic index (SSI), relative reaction time (RRT) and nerve conduction velocity (NCV) in Clobetasol/GSC group are -74.55, 1.30, and 46.4 mm/s at Week 12, respectively, while these parameters are -64.53, 1.23, and 49.8 mm/s in Autograft group. Thus, this work represents the first report unveiling clobetasol's potential in peripheral nerve regeneration, reveals the feasibility of applying a sericin conduit for repairing a large nerve defect, and demonstrates the effectiveness of the clobetasol-loaded-GSC based strategy in transected nerves' regeneration.
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- 2021
44. Ginsenoside Compound K Promotes Proliferation, Migration and Differentiation of Schwann Cells via the Activation of MEK/ERK1/2 and PI3K/AKT Pathways
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Huimin He, Fangfei Qu, Lijun Du, Hao Wang, Wei Sun, and Ting Xin
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0301 basic medicine ,Ginsenosides ,MAP Kinase Signaling System ,Biochemistry ,Schwann cell proliferation ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,0302 clinical medicine ,Western blot ,Cell Movement ,medicine ,Animals ,LY294002 ,Remyelination ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,medicine.diagnostic_test ,biology ,Cell growth ,Cell Differentiation ,General Medicine ,Myelin basic protein ,Cell biology ,Rats ,Phosphotransferases (Alcohol Group Acceptor) ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,chemistry ,biology.protein ,Schwann Cells ,030217 neurology & neurosurgery - Abstract
The proliferation and differentiation of Schwann cells are critical for the remyelination of injured peripheral nerve. Ginsenoside compound K (CK) is a metabolite produced from ginsenoside Rb1 which has strong anti-inflammatory effects. However, the potential effects of CK on Schwann cells have not been studied systematically before. Therefore, this study was aimed to explore the functions of CK in Schwann cell proliferation, migration and differentiation and its potential regulatory mechanism. Primary Schwann cells and RSC96 cells were treated with or without CK at different doses. The proliferation and migration of primary Schwann cells and RSC96 cells were examined by Cell Counting Kit-8 (CCK-8) and Transwell assays, respectively. The mRNA expression of myelin-associated glycoprotein (MAG) and myelin basic protein (MBP) was tested by quantitative real-time polymerase chain reaction (qRT-PCR). The levels of all proteins were examined by Western blot. CK could promote cell proliferation, migration and induce MAG and MBP expression in primary Schwann cells and RSC96 cells. Furthermore, CK activated MEK/ERK1/2 and PI3K/AKT pathways, and the beneficial effects of CK on primary Schwann cells and RSC96 cells were distinctly suppressed by inhibitor PD98059 or LY294002. Ginsenoside compound K induced cell proliferation, migration and differentiation via the activation of MEK/ERK1/2 and PI3K/AKT pathways in cultured primary Schwann cells and RSC96 cells.
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- 2020
45. MiR-34a regulates Schwann cell proliferation and migration by targeting CNTN2
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Yong Zhao, Xiaobing Jiang, Jianqing Liu, Xiaobin Zhou, and Dexin Zou
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0301 basic medicine ,Male ,Schwann cell proliferation ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,Dorsal root ganglion ,Downregulation and upregulation ,Cell Movement ,Ganglia, Spinal ,medicine ,Contactin 2 ,Animals ,Cell Proliferation ,Gene knockdown ,Cell growth ,Chemistry ,General Neuroscience ,Regeneration (biology) ,Sciatic nerve injury ,medicine.disease ,Cell biology ,Nerve Regeneration ,Rats ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,Peripheral nerve injury ,Schwann Cells ,Sciatic Neuropathy ,030217 neurology & neurosurgery - Abstract
The proliferation and migration of Schwann cells contribute to axonal outgrowth and functional recovery after peripheral nerve injury. Previously, several microRNAs were abnormally expressed after peripheral nerve injury and they played important roles in peripheral nerve regeneration. However, the role and underlying mechanism of miR-34a in peripheral nerve injury remain largely unknown. The levels of miR-34a and contactin-2 (CNTN2) were detected by quantitative real-time PCR. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide and transwell assays were used to examine cell proliferation and migration, respectively. The protein level of CNTN2 was measured by western blot. The binding sites of miR-34a and CNTN2 were predicted by the online software and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Following sciatic nerve injury, the expression of miR-34a was downregulated in the crushed nerve segment, reaching a minimum at the seventh day. Knockdown of miR-34a enhanced the axon outgrowth of dorsal root ganglion neurons. Moreover, miR-34a overexpression evidently inhibited the proliferation of Schwann cells, whereas its knockdown showed the opposite effects. In addition, CNTN2 was a direct target of miR-34a and its expression was negatively regulated by miR-34a in the crushed nerve segment. Besides, CNTN2 overexpression or knockdown could reverse the effects of miR-34a upregulation or downregulation on proliferation and migration of Schwann cells, respectively. Collectively, miR-34a inhibited the proliferation and migration of Schwann cells via targeting CNTN2, which might provide a new approach to peripheral nerve regeneration.
- Published
- 2020
46. Author response for 'Melatonin promotes Schwann cell proliferation and migration via the shh signalling pathway after peripheral nerve injury'
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Bu Xiangbo, Li Jing, Gao Xiao, Menghan Cao, Bin Pan, Kaijin Guo, Li Zi'ang, Hu Feng, and Youzhong Hu
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Melatonin ,Peripheral nerve injury ,medicine ,Biology ,Hedgehog signaling pathway ,Schwann cell proliferation ,Cell biology ,medicine.drug - Published
- 2020
47. Review for 'Melatonin promotes Schwann cell proliferation and migration via the shh signalling pathway after peripheral nerve injury'
- Author
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Sadrettin Pence
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Melatonin ,Peripheral nerve injury ,medicine ,Biology ,Hedgehog signaling pathway ,Schwann cell proliferation ,medicine.drug ,Cell biology - Published
- 2020
48. Review for 'Melatonin promotes Schwann cell proliferation and migration via the shh signalling pathway after peripheral nerve injury'
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Arash Zaminy
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Melatonin ,Peripheral nerve injury ,medicine ,Biology ,Hedgehog signaling pathway ,Cell biology ,medicine.drug ,Schwann cell proliferation - Published
- 2020
49. SPP1 Promotes Schwann Cell Proliferation and Survival through PKCα by Binding with CD44 and αvβ3 after Peripheral Nerve Injury
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Shusen Cui, Tuo Yang, Shuang Du, Rang-Juan Cao, Jian-Nan Li, Jiangbo Wang, and Zhan Zhang
- Subjects
0301 basic medicine ,Wallerian degeneration ,lcsh:Biotechnology ,General Biochemistry, Genetics and Molecular Biology ,Schwann cell proliferation ,lcsh:Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,lcsh:TP248.13-248.65 ,medicine ,Schwann cells ,lcsh:QD415-436 ,Osteopontin ,CD44 ,lcsh:QH301-705.5 ,Cell proliferation ,biology ,integumentary system ,Chemistry ,Research ,PKCα ,medicine.disease ,αvβ3 ,Cell biology ,030104 developmental biology ,lcsh:Biology (General) ,nervous system ,Apoptosis ,Peripheral nerve injury ,030220 oncology & carcinogenesis ,biology.protein ,Cell apoptosis ,Signal transduction ,tissues ,SPP1 - Abstract
Background Schwann cells (SCs) play a crucial role in Wallerian degeneration after peripheral nerve injury. The expression of genes in SCs undergo a series of changes, which greatly affect the proliferation and apoptosis of SCs as well as the fate of peripheral nerve regeneration. However, how do these genes regulate the proliferation and apoptosis of SCs remains unclear. Results SPP1 and PKCα were found upregulated after human median peripheral nerve injury, which promoted SCs proliferation and survival. The promoted proliferation and inhibited apoptosis by SPP1 were blocked after the treatment of PKCα antagonist Gö6976. Whereas, the inhibited proliferation and enhanced apoptosis induced by silence of SPP1 could be rescued by the activation of PKCα, which suggested that SPP1 functioned through PKCα. Moreover, both CD44 and αvβ3 were found expressed in SCs and increased after peripheral nerve injury. Silence of CD44 or β3 alleviated the increased proliferation and inhibited apoptosis induced by recombinant osteopontin, suggesting the function of SPP1 on SCs were dependent on CD44 and β3. Conclusion These results suggested that SPP1 promoted proliferation and inhibited apoptosis of SCs through PKCα signaling pathway by binding with CD44 and αvβ3. This study provides a potential therapeutic target for improving peripheral nerve recovery.
- Published
- 2020
50. TNFα promotes oral cancer growth, pain, and Schwann cell activation
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Nguyen Huu Tu, Zinaida Dubeykovskaya, Bradley E. Aouizerat, Shruti A. Chavan, Yi Ye, Nicole N. Scheff, and Elizabeth Salvo
- Subjects
medicine.medical_treatment ,Science ,Schwann cell ,Article ,Schwann cell proliferation ,Mice ,Mediator ,Nerve Growth Factor ,medicine ,Animals ,Humans ,Cancer ,Cell Proliferation ,Pain Measurement ,Multidisciplinary ,business.industry ,Tumor Necrosis Factor-alpha ,Cancer Pain ,medicine.disease ,Nerve growth factor ,medicine.anatomical_structure ,Nociception ,Cytokine ,nervous system ,Cancer research ,Disease Progression ,Medicine ,Tumor necrosis factor alpha ,Mouth Neoplasms ,Schwann Cells ,business ,Neuroscience - Abstract
Oral cancer is very painful and impairs a patient’s ability to eat, talk, and drink. Mediators secreted from oral cancer can excite and sensitize sensory neurons inducing pain. Cancer mediators can also activate Schwann cells, the peripheral glia that regulates neuronal function and repair. The contribution of Schwann cells to oral cancer pain is unclear. We hypothesize that the oral cancer mediator TNFα activates Schwann cells, which further promotes cancer progression and pain. We demonstrate that TNFα is overexpressed in human oral cancer tissues and correlates with increased self-reported pain in patients. Antagonizing TNFα reduces oral cancer proliferation, cytokine production, and nociception in mice with oral cancer. Oral cancer or TNFα alone increases Schwann cell activation (measured by Schwann cell proliferation, migration, and activation markers), which can be inhibited by neutralizing TNFα. Cancer- or TNFα-activated Schwann cells release pro-nociceptive mediators such as TNFα and nerve growth factor (NGF). Activated Schwann cells induce nociceptive behaviors in mice, which is alleviated by blocking TNFα. Our study suggests that TNFα promotes cancer proliferation, progression, and nociception at least partially by activating Schwann cells. Inhibiting TNFα or Schwann cell activation might serve as therapeutic approaches for the treatment of oral cancer and associated pain.
- Published
- 2020
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