Long noncoding RNA GAS5 inhibits cell proliferation and fibrosis in diabetic nephropathy by sponging miR-221 and modulating SIRT1 expression

被引：93

作者：

Ge, Xiaoxu ^{[1
]}

Xu, Bojin ^{[1
]}

Xu, Wenwei ^{[2
]}

Xia, Lili ^{[1
]}

Xu, Zhongqin ^{[3
]}

Shen, Lisha ^{[1
]}

Peng, Wenfang ^{[1
]}

Huang, Shan ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Dept Endocrinol, Tongren Hosp, Shanghai, Peoples R China

[2] Shanghai Jiao Tong Univ, Dept Geriatr, Tongren Hosp, Shanghai, Peoples R China

[3] Shanghai Jiao Tong Univ, Dept Family Med, Tongren Hosp, Shanghai, Peoples R China

来源：

AGING-US | 2019年 / 11卷 / 20期

关键词：

diabetic nephropathy; proliferation; fibrosis; lncRNA GAS5; TO-MESENCHYMAL TRANSITION; OXIDATIVE STRESS; RETINOPATHY;

D O I：

10.18632/aging.102249

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Diabetic nephropathy (DN) is one of the leading causes of end-stage renal diseases worldwide. This study is designed to investigate the underlying function and mechanism of a novel lncRNA GAS5 in the progression of DN. We found that lncRNA GAS5 expression level was decreased in type 2 diabetes (T2D) with DN compared with that in patients without DN. Moreover, lncRNA GAS5 expression level was negatively associated with the severity of DN-related complications. lncRNA GAS5 inhibited MCs proliferation and caused G0/1 phase arrest. lncRNA GAS5 overexpression alleviated the expression of fibrosis-related protein in mesangial cells (MCs). The dual-luciferase reporter assay and RNA binding protein immunoprecipitation (RIP) assay results revealed that lncRNA GAS5 functions as an endogenous sponge for miR-221 via both the directly targeting way and Ago2-dependent manner. Furthermore, SIRT1 was confirmed as a target gene of miR-221. lncRNA GAS5 upregulated SIRT1 expression and inhibited MCs proliferation and fibrosis by acting as an miR-221 sponge. Finally, we found that lncRNA GSA5 suppressed the development of DN in vivo. Thus, lncRNA GAS5 was involved in the progression of DN by sponging miR-221 and contributed to lncRNA- directed diagnostics and therapeutics in DN.

引用

页码：8745 / 8759

页数：15

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