Loss of lncRNA MIAT ameliorates proliferation and fibrosis of diabetic nephropathy through reducing E2F3 expression. Issue 22 (3rd October 2020)

• Record Type: Journal Article
• Authors: Ji, Ting‐Ting; Qi, Ying‐Hui; Li, Xiao‐Ying; Tang, Bo; Wang, Ya‐Kun; Zheng, Peng‐Xi; Li, Weiliang; Qu, Xiaolei; Feng, Linhong; Bai, Shou‐Jun
• Is Part Of: Journal of cellular and molecular medicine. Volume 24:Issue 22(2020)
• Page Start: 13314
• Page End: 13323
• Publication Date: 2020-10-03
• Subjects: diabetic nephropathy -- E2F3 -- MIAT -- miR‐147a; Cytology; Medicine; Molecular Biology; Cytologie -- Périodiques; Médecine -- Périodiques; Biologie moléculaire -- Périodiques; Cytology -- Periodicals; Medicine -- Periodicals; Molecular biology -- Periodicals; 611.01805
• DOI: 10.1111/jcmm.15949
• Languages: English
• ISSNs: 1582-1838

Abstract

Abstract: Diabetic nephropathy (DN) is a serious kidney disease resulted from diabetes. Dys‐regulated proliferation and extracellular matrix (ECM) accumulation in mesangial cells contribute to DN progression. In this study, we tested expression level of MIAT in DN patients and mesangial cells treated by high glucose (HG). Up‐regulation of MIAT was observed in DN. Then, functional assays displayed that silence of MIAT by siRNA significantly repressed the proliferation and cycle progression in mesangial cells induced by HG. Meanwhile, we found that collagen IV, fibronectin and TGF‐β1 protein expression was obviously triggered by HG, which could be rescued by loss of MIAT. Then, further assessment indicated that MIAT served as sponge harbouring miR‐147a. Moreover, miR‐147a was decreased in DN, which exhibited an antagonistic effect of MIAT on modulating mesangial cell proliferation and fibrosis. Moreover, bioinformatics analysis displayed that E2F transcription factor 3 (E2F3) could act as direct target of miR‐147a. We demonstrated that E2F3 was greatly increased in DN and the direct binding association between miR‐147a and E2F3 was evidenced using luciferase reporter assay. In summary, our data explored the underlying mechanism of DN pathogenesis validated that MIAT induced mesangial cell proliferation and fibrosis via sponging miR‐147a and regulating E2F3.