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154 results on '"Zhao, Ludan"'

3. Tissue Repair in the Mouse Liver Following Acute Carbon Tetrachloride Depends on Injury‐Induced Wnt/β‐Catenin Signaling

Author

Zhao, Ludan, Jin, Yinhua, Donahue, Katie, Tsui, Margaret, Fish, Matt, Logan, Catriona Y, Wang, Bruce, and Nusse, Roel

Subjects
Regenerative Medicine, Digestive Diseases, Liver Disease, 2.1 Biological and endogenous factors, Aetiology, Animals, Axin Protein, Biopsy, Needle, Carbon Tetrachloride, Cells, Cultured, Disease Models, Animal, Gene Expression, Hepatocytes, Immunohistochemistry, Liver, Liver Regeneration, Male, Mice, Mice, Inbred C57BL, Polymerase Chain Reaction, RNA, Random Allocation, Reference Values, Wnt Proteins, Wnt Signaling Pathway, beta Catenin, Medical Biochemistry and Metabolomics, Clinical Sciences, Immunology, Gastroenterology & Hepatology
Abstract

In the liver, Wnt/β-catenin signaling is involved in regulating zonation and hepatocyte proliferation during homeostasis. We examined Wnt gene expression and signaling after injury, and we show by in situ hybridization that Wnts are activated by acute carbon tetrachloride (CCl4 ) toxicity. Following injury, peri-injury hepatocytes become Wnt-responsive, expressing the Wnt target gene axis inhibition protein 2 (Axin2). Lineage tracing of peri-injury Axin2+ hepatocytes shows that during recovery the injured parenchyma becomes repopulated and repaired by Axin2+ descendants. Using single-cell RNA sequencing, we show that endothelial cells are the major source of Wnts following acute CCl4 toxicity. Induced loss of β-catenin in peri-injury hepatocytes results in delayed repair and ultimately injury-induced lethality, while loss of Wnt production from endothelial cells leads to a delay in the proliferative response after injury. Conclusion: Our findings highlight the importance of the Wnt/β-catenin signaling pathway in restoring tissue integrity following acute liver toxicity and establish a role of endothelial cells as an important Wnt-producing regulator of liver tissue repair following localized liver injury.

Published
2019

12. Self-renewing diploid Axin2+ cells fuel homeostatic renewal of the liver

Author

Wang, Bruce, Zhao, Ludan, Fish, Matt, Logan, Catriona Y, and Nusse, Roel

Subjects
Stem Cell Research, Liver Disease, Digestive Diseases, 1.1 Normal biological development and functioning, Underpinning research, Oral and gastrointestinal, Animals, Axin Protein, Biomarkers, Cell Lineage, Cell Proliferation, Clone Cells, Diploidy, Endothelial Cells, Female, Hepatocytes, Homeostasis, Liver, Male, Mice, Polyploidy, Regeneration, Staining and Labeling, Stem Cell Niche, Stem Cells, T-Box Domain Proteins, Time Factors, Veins, Wnt Signaling Pathway, General Science & Technology
Abstract

The source of new hepatocytes in the uninjured liver has remained an open question. By lineage tracing using the Wnt-responsive gene Axin2 in mice, we identify a population of proliferating and self-renewing cells adjacent to the central vein in the liver lobule. These pericentral cells express the early liver progenitor marker Tbx3, are diploid, and thereby differ from mature hepatocytes, which are mostly polyploid. The descendants of pericentral cells differentiate into Tbx3-negative, polyploid hepatocytes, and can replace all hepatocytes along the liver lobule during homeostatic renewal. Adjacent central vein endothelial cells provide Wnt signals that maintain the pericentral cells, thereby constituting the niche. Thus, we identify a cell population in the liver that subserves homeostatic hepatocyte renewal, characterize its anatomical niche, and identify molecular signals that regulate its activity.

Published
2015

34. Hierarchical core–shell nanoplatforms constructed from Fe3O4@C and metal–organic frameworks with excellent bilirubin removal performance.

Author

Gan, Na, Sun, Qiaomei, Zhao, Ludan, Zhang, Shuangshuang, Suo, Zili, Wang, Xinlong, and Li, Hui

Abstract

Hemoperfusion has become the third-generation treatment strategy for patients suffering from hyperbilirubinemia, but adsorbents used for bilirubin removal mostly face intractable problems, such as unsatisfactory adsorption performance and poor hemocompatibility. Metal–organic frameworks (MOFs) are promising adsorbents for hemoperfusion due to their high specific surface areas and easily modified organic ligands. However, their microporous properties and separation have hampered their application. Here, a novel hierarchical core–shell nanoplatform (named Double-PEG) with tailored binding sites and pore sizes based on Fe3O4@C and Uio66-NH2 was constructed. Notably, Double-PEG showed excellent bilirubin uptake of up to 1738.30 mg g−1 and maintained excellent bilirubin removal efficiency in simulated biological solutions. A study on the adsorption mechanism showed that the adsorption of Double-PEG towards bilirubin tended to be chemical adsorption and in accordance with the Langmuir model. Besides, the good separability, recyclability, cytotoxicity and hemocompatibility of Double-PEG show great potential in hemoperfusion therapy. The finding of this study may provide a novel insight into the application of MOF materials in the field of hemoperfusion. [ABSTRACT FROM AUTHOR]

Published
2021
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