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Lysyl oxidase-mediated elastin upregulation promotes the proliferation and migration of human retinal endothelial cells.
- Source :
-
Advances in clinical and experimental medicine : official organ Wroclaw Medical University [Adv Clin Exp Med] 2024 Jun; Vol. 33 (6), pp. 641-651. - Publication Year :
- 2024
-
Abstract
- Background: Proliferative diabetic retinopathy (PDR) is a major cause of irreversible blindness in the working age population. The dysfunction of retinal vascular endothelial cells (RVECs) is the primary cause of PDR. Extracellular matrix (ECM) accumulation promotes intracellular signaling required for RVEC proliferation, migration, survival, and tube morphogenesis.<br />Objectives: This study aimed to investigate the role of lysyl oxidase (LOX) in the cellular function of RVECs and PDR pathogenesis and to identify the underlying mechanisms.<br />Material and Methods: Protein expression was determined with western blot. The interaction between LOX and elastin (ELN) was detected using a co-immunoprecipitation (Co-IP) assay, and the Cell Counting Kit-8 (CCK-8) assay evaluated cell viability. A colony formation assay was employed to assess the proliferation of human RVECs (hRVECs), and a transwell assay to determine their migration ability. Streptozotocin was used to establish PDR in mice in vivo. A histological analysis was conducted using hematoxylin and eosin (H&E) staining.<br />Results: The results showed that LOX was overexpressed in PDR patients. The LOX knockdown suppressed ECM formation and hRVEC proliferation and migration. Additionally, LOX upregulated ELN expression. However, overexpressed ELN promoted hRVEC proliferation and migration. In vivo experiments showed that curcumin-mediated LOX deficiency restored retinal tissue structure.<br />Conclusions: The LOX-knockdown suppressed ECM formation and hRVEC proliferation and migration by inactivating ELN. Therefore, LOX/ELN signaling may be a potential PDR biomarker.
- Subjects :
- Humans
Animals
Mice
Male
Retina metabolism
Retina pathology
Middle Aged
Cells, Cultured
Female
Cell Proliferation
Cell Movement
Protein-Lysine 6-Oxidase metabolism
Protein-Lysine 6-Oxidase genetics
Endothelial Cells metabolism
Endothelial Cells pathology
Endothelial Cells enzymology
Elastin metabolism
Diabetic Retinopathy pathology
Diabetic Retinopathy metabolism
Diabetic Retinopathy genetics
Up-Regulation
Subjects
Details
- Language :
- English
- ISSN :
- 1899-5276
- Volume :
- 33
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Advances in clinical and experimental medicine : official organ Wroclaw Medical University
- Publication Type :
- Academic Journal
- Accession number :
- 38353503
- Full Text :
- https://doi.org/10.17219/acem/170999