circRNA_010383 acts as a sponge for miR-135a and its downregulated expression contributes to renal fibrosis in diabetic nephropathy
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posted on 2020-11-17, 22:53 authored by Ada AdminAda Admin, Fenfen Peng, Wangqiu Gong, Shuting Li, Bohui Yin, Chen Zhao, Wenting Liu, Xiaowen Chen, Congwei Luo, Qianying Huang, Ting Chen, Lingzhi Sun, Shun Fang, Weidong Zhou, Zhijian Li, Haibo LongDiabetic 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 promoted proteinuria and renal fibrosis in DN by acting as a sponge
for miRNA-135a. This study reveals that circRNA_010383 may be a novel
therapeutic target for DN in the future.
