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MiR‐203a‐3p inhibits retinal angiogenesis and alleviates proliferative diabetic retinopathy in oxygen‐induced retinopathy (OIR) rat model via targeting VEGFA and HIF‐1α
Author(s) -
Han Ning,
Xu Haitao,
Yu Na,
Wu Yazhen,
Yu Li
Publication year - 2020
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.13163
Subject(s) - angiogenesis , retinal , diabetic retinopathy , vascular endothelial growth factor a , downregulation and upregulation , retinopathy , retina , chemistry , medicine , vascular endothelial growth factor , endocrinology , biology , diabetes mellitus , ophthalmology , biochemistry , vegf receptors , neuroscience , gene
Proliferative diabetic retinopathy (PDR) is a common complication of diabetes mellitus, characterized by abnormal retinal angiogenesis. MicroRNA‐203‐3p (miR‐203‐3p) was found to be down‐regulated in a murine model of proliferative retinopathy. This study was performed to explore the role of miR‐203a‐3p in retinal angiogenesis of PDR. Firstly, a rat OIR model, which was used to mimic PDR, was established and the OIR rats were treated with scrambled control or miR‐203a‐3p agomir by intravitreal injection. The results showed that the level of miR‐203a‐3p was decreased in OIR rats, and forced over‐expression of miR‐203a‐3p inhibited OIR‐induced retinal angiogenesis as evidenced by reduced blood vessel profiles and CD31 expression. OIR‐induced up‐regulation of VEGFA, HIF‐α, PCNA, and MMPs in the retina was also counteracted by miR‐203a‐3p. Additionally, high glucose (HG)‐induced proliferation, migration and tube formation of human retinal microvascular endothelial cells (HRMECs) were also dampened by the up‐regulation of miR‐203a‐3p. Dual‐luciferase reporter assay showed that miR‐203a‐3p could specifically bind to the 3′UTR of VEGFA and HIF‐1α. Over‐expression of VEGFA or HIF‐1α restored the tube formation activity of HRMECs suppressed by miR‐203a‐3p. In conclusion, our findings demonstrate that up‐regulation of miR‐203a‐3p might inhibit pathological retinal angiogenesis of PDR by targeting VEGFA and HIF‐1α.