circRNA_010383 Acts as a Sponge for miR-135a and its Downregulated Expression Contributes to Renal Fibrosis in Diabetic Nephropathy

Diabetes
Fenfen PengHaibo Long

Abstract

Diabetic nephropathy (DN), a vascular complication of diabetes mellitus, is the leading cause of death in diabetic patients. The contribution of aberrantly expressed circRNAs to diabetic nephropathy in vivo is poorly understood. Integrated comparative circRNA microarray profiling was used to examine the expression of circRNAs in diabetic kidney of db/db mice. We found that circRNA_010383 expression was markedly downregulated in diabetic kidneys, mesangial cells and tubular epithelial cells cultured in high-glucose conditions. circRNA_010383 colocalized with microRNA-135a (miR-135a) and inhibited miR-135a function by directly binding to miR-135a. In vitro, the knockdown of circRNA_010383 promoted the accumulation of extracellular matrix (ECM) proteins and downregulated the expression of transient receptor potential cation channel, subfamily C, member (TRPC1), which is a target protein of miR-135a. Furthermore, circRNA_010383 overexpression effectively inhibited the high-glucose-induced accumulation of ECM and increased TRPC1 levels in vitro More importantly, the kidney-target of circRNA_010383 overexpression inhibited proteinuria and renal fibrosis in db/db mice. Mechanistically, we identified that a loss of circRNA_010383 promo...Continue Reading

Citations

Feb 22, 2021·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Xiaoniu DaiJie Chao
Mar 30, 2021·Frontiers in Pharmacology·Xin-Tian ChenJin Bai
Jun 13, 2021·Ageing Research Reviews·Yang YangYe Tian
Jul 3, 2021·International Journal of Molecular Sciences·Swayam Prakash SrivastavaDaisuke Koya
Jul 4, 2021·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Jiang LiuJuanjuan Jiang

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