Osteopontin Upregulates Col IV Expression by Repressing miR-29a in Human Retinal Capillary Endothelial Cells.

Abstract:

:Abnormal synthesis of extracellular matrix (ECM), especially collagen type IV (Col IV), in human retinal capillary endothelial cells (HRCECs) and resultant basement membrane (BM) thickening is the most prominent and characteristic feature of early diabetic retinopathy (DR). Osteopontin (OPN) has been shown to play an important role in the pathogenesis of DR and specifically, found to be critically involved in diabetic nephropathy, as it can upregulate many factors, like collagen IV. However, the precise role of OPN in the pathogenesis of DR and the underlying mechanisms remain unclear. In this study, 51 differentially expressed microRNAs (miRNAs; 42 miRNAs upregulated and 9 miRNAs downregulated) were first identified in retina of streptozotocin (STZ)-induced diabetic mice with DR. Among these miRNAs, we identified miRNA (miR)-29a as a prominent miRNA that targeted and directly downregulated Col IV expression through database prediction and dual-luciferase reporter assay, which was further confirmed in HRCECs using miR-29a mimic, miR-29a inhibitor, and pre-miR-29a transfection. Furthermore, OPN upregulated Col IV expression via a miR-29a-repressed pathway in HRCECs. Taken together, these results provided a miR-29a-repressing mechanism through which OPN plays roles in abnormal synthesis of Col IV in HRCECs and resultant BM thickening, contributing to the pathogenesis of DR.

journal_name

Mol Ther Nucleic Acids

authors

Duan P,Chen S,Zeng Y,Xu H,Liu Y

doi

10.1016/j.omtn.2020.02.001

subject

Has Abstract

pub_date

2020-06-05 00:00:00

pages

242-251

issn

2162-2531

pii

S2162-2531(20)30073-1

journal_volume

20

pub_type

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