Journal
ACTA DIABETOLOGICA
Volume 57, Issue 12, Pages 1435-1443Publisher
SPRINGER-VERLAG ITALIA SRL
DOI: 10.1007/s00592-020-01569-7
Keywords
MiR-148a-3p; Diabetic retinopathy; TGFB2; FGF2
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Funding
- Affiliated Hospital of Jiangnan University
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Aims Diabetic retinopathy (DR), a common complication of type 1 or type 2 diabetes mellitus, has become the leading cause of blindness among adults in working age. The dysregulation of microRNA has been reported to be strongly related to the initiation or progression of DR. However, neither the biological role nor the molecular mechanism of miR-148a-3p has been researched in DR. This study is designed to investigate the function and mechanism of miR-148a-3p in DR. Methods The bioinformatics analysis (Targetscan: https://www.targetscan.org/vert_72/) and numerous experiments including real-time quantitative polymerase chain reaction, terminal deoxynucleotidyltransferase dUTP nick end labeling, CCK-8, western blot, vasculogenesis and luciferase reporter assays were used to research the function and mechanism of miR-148a-3p in DR. Results We constructed DR cell model by treating human retinal microvascular endothelial cells (HRECs) with different concentration gradients of high glucose (HG). Additionally, HG treatment reduced miR-148a-3p level in HRECs. In function, overexpression of miR-148a-3p caused an increase in cell viability and a decrease in cell apoptosis. Besides, miR-148a-3p overexpression led to a damage on blood-retinal barrier (BRB) and suppressed angiogenesis. In mechanism, miR-148a-3p specifically bound to 3' untranslated region of TGFB2 and FGF2. At least, rescue assays demonstrated that the inhibitive influence of miR-148a-3p mimics on BRB injury was offset by overexpression of TGFB2 and the attenuation of angiogenesis resulting from miR-148a-3p mimics was abrogated by overexpression of FGF2 Conclusions In a word, we discovered that miR-148a-3p alleviated HG-induced DR by targeting TGFB2 and FGF2. This novel discovery indicated miR-148a-3p as a potential target for DR diagnosis or treatment.
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