In:
Bioscience Reports, Portland Press Ltd., Vol. 40, No. 11 ( 2020-11-27)
Abstract:
Increasing evidence has shown that microRNAs (miRNAs) play an important role in the pathogenesis of diabetic retinopathy (DR). However, the role and mechanism of miRNA in regulating high glucose (HG)-induced ARPE-19 cell injury are still not well understood. The present study aimed to investigate the effects of miR-200a-3p on DR progression and reveal the underlying mechanisms of their effects. In the present study, we observed that miR-200a-3p was significantly decreased, while transforming growth factor-β2 (TGF-β2) expression was up-regulated in ARPE-19 cells treated with HG and retina tissues of DR rats. Subsequently, overexpression of miR-200a-3p significantly promoted cell proliferation, reduced apoptosis, as well as inhibited the levels of inflammatory cytokines secreted, matrix metalloprotease 2/9 (MMP2/9), and vascular endothelial growth factor (VEGF) in HG-injured ARPE-19 cells. Moreover, miR-200a-3p was proved to target TGF-β2 mRNA by binding to its 3′ untranslated region (3′UTR) using a luciferase reporter assay. Mechanistically, overexpression of miR-200a-3p reduced HG-induced ARPE-19 cell injury and reduced inflammatory cytokines secreted, as well as down-regulated the expression of VEGF via inactivation of the TGF-β2/Smad pathway in vitro. In vivo experiments, up-regulation of miR-200a-3p ameliorated retinal neovascularization and inflammation of DR rats. In conclusion, our findings demonstrated that miR-200a-3p-elevated prevented DR progression by blocking the TGF-β2/Smad pathway, providing a new therapeutic biomarker for DR treatment in the clinic.
Type of Medium:
Online Resource
ISSN:
0144-8463
,
1573-4935
Language:
English
Publisher:
Portland Press Ltd.
Publication Date:
2020
detail.hit.zdb_id:
2014993-1
SSG:
12
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