Research Paper Volume 11, Issue 20 pp 8745—8759

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

Xiaoxu Ge 1, *, , Bojin Xu 1, *, , Wenwei Xu 2, *, , Lili Xia 1, , Zhongqin Xu 3, , Lisha Shen 1, , Wenfang Peng 1, , Shan Huang 1, ,

  • 1 Department of Endocrinology, Tongren Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China
  • 2 Department of Geriatrics, Tongren Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China
  • 3 Department of Family Medicine, Tongren Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China
* Equal contribution

received: May 19, 2019 ; accepted: September 2, 2019 ; published: October 20, 2019 ;

https://doi.org/10.18632/aging.102249
How to Cite

Copyright © 2019 Ge et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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.

Abbreviations

DN: Diabetic nephropathy; FISH: Fluorescence in situ hybridization; CCK-8: Cell Counting Kit-8; qPCR: Quantitative reverse transcription polymerase chain reaction; ceRNA: Competing endogenous RNA; EdU: Ethynyl-2-deoxyuridine; lncRNA: Long non-coding RNA; EMT: epithelial-mesenchymal transition; MCs: mesangial cells.