LncRNA lnc-ISG20 promotes renal fibrosis in diabetic nephropathy by inducing AKT phosphorylation through miR-486-5p/NFAT5

被引:33
作者
Duan, Yu-Rui [1 ]
Chen, Bao-Ping [1 ]
Chen, Fang [1 ]
Yang, Su-Xia [1 ]
Zhu, Chao-Yang [1 ]
Ma, Ya-Li [1 ]
Li, Yang [2 ]
Shi, Jun [1 ]
机构
[1] Henan Univ, Dept Nephrol, Huaihe Hosp, 8 Baobei Rd, Kaifeng, Peoples R China
[2] Henan Univ, Dept Urol, Huaihe Hosp, Kaifeng, Peoples R China
关键词
AKT; diabetic nephropathy; fibrosis; Lnc‐ ISG20; MicroRNA‐ 486‐ 5p; NFAT5; GENE-EXPRESSION; CELL; CANCER; MICRORNAS; APOPTOSIS; PATHWAYS;
D O I
10.1111/jcmm.16280
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Long non-coding RNA (lncRNA) lnc-ISG20 has been found aberrantly up-regulated in the glomerular in the patients with diabetic nephropathy (DN). We aimed to elucidate the function and regulatory mechanism of lncRNA lnc-ISG20 on DN-induced renal fibrosis. Expression patterns of lnc-ISG20 in kidney tissues of DN patients were determined by RT-qPCR. Mouse models of DN were constructed, while MCs were cultured under normal glucose (NG)/high glucose (HG) conditions. The expression patterns of fibrosis marker proteins collagen IV, fibronectin and TGF-beta 1 were measured with Western blot assay. In addition, the relationship among lnc-ISG20, miR-486-5p, NFAT5 and AKT were analysed using dual-luciferase reporter assay and RNA immunoprecipitation. The effect of lnc-ISG20 and miR-486/NFAT5/p-AKT axis on DN-associated renal fibrosis was also verified by means of rescue experiments. The expression levels of lnc-ISG20 were increased in DN patients, DN mouse kidney tissues and HG-treated MCs. Lnc-ISG20 silencing alleviated HG-induced fibrosis in MCs and delayed renal fibrosis in DN mice. Mechanistically, miR-486-5p was found to be a downstream miRNA of lnc-ISG20, while miR-486-5p inhibited the expression of NFAT5 by binding to its 3'UTR. NFAT5 overexpression aggravated HG-induced fibrosis by stimulating AKT phosphorylation. However, NFAT5 silencing reversed the promotion of in vitro and in vivo fibrosis caused by lnc-ISG20 overexpression. Our collective findings indicate that lnc-ISG20 promotes the renal fibrosis process in DN by activating AKT through the miR-486-5p/NFAT5 axis. High-expression levels of lnc-ISG20 may be a useful indicator for DN.
引用
收藏
页码:4922 / 4937
页数:16
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