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  • Title: In vitro protective effect of miR-181d-5p in high glucose‑induced human retinal microvascular endothelial cells by targeting the angiogenic factor VEGFA.
    Author: Wang F, Yu C.
    Journal: Eur Rev Med Pharmacol Sci; 2022 Sep; 26(17):6199-6207. PubMed ID: 36111920.
    Abstract:
    OBJECTIVE: Previous studies show the downregulation of miR-181d-5p in the vitreous humor of patients with diabetic retinopathy (DR); however, it is not known whether miR-181d-5p is implicated in the development of DR. The present study aimed at evaluating the beneficial effects of miR-181d-5p on high glucose (HG)‑induced human retinal microvascular endothelial cells (hRMECs), as well as the underlying mechanism. MATERIALS AND METHODS: hRMECs treated with HG were used to induce an in vitro cell model of DR. The analysis of quantitative real-time PCR (qRT-PCR) and western blot were used to detect the expression of miR-181d-5p and vascular endothelial growth factor A (VEGFA). The cell viability was measured using CCK-8 assay. The migration was assessed by performing Transwell assay. The angiogenesis of hRMECs was evaluated using the tube formation assay. The binding between target genes was explored using bioinformatic prediction and the luciferase reporter assay. RESULTS: HG treatment decreased miR-181d-5p but upregulated VEGFA expression in hRMECs. MiR-181d-5p inhibition augmented cell proliferation, migration and angiogenesis of hRMECs caused by HG. Upregulation of miR-181d-5p led to opposing effects, and miR-181d-5p directly targeted and negatively regulated VEGFA. The overexpression of VEGFA reversed the anti-proliferative, anti-migratory and antiangiogenic effects of miR-181d-5p in HG-treated hRMECs. CONCLUSIONS: These findings indicate that miR-181d-5p ameliorates HG-stimulated proliferation, migration and angiogenesis of hRMECs through inhibition of VEGFA, which might provide a new target for the treatment of DR.
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