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

• Published in: Aging (Albany, NY.) Vol. 11; no. 20; pp. 8745 - 8759
• Main Authors: Ge, Xiaoxu, Xu, Bojin, Xu, Wenwei, Xia, Lili, Xu, Zhongqin, Shen, Lisha, Peng, Wenfang, Huang, Shan
• Format: Journal Article
• Language: English
• Published: United States Impact Journals 20.10.2019
• Subjects: Research Paper; fibrosis; proliferation; diabetic nephropathy; lncRNA GAS5
• ISSN: 1945-4589; 1945-4589
• DOI: 10.18632/aging.102249

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.