Research Paper Volume 11, Issue 11 pp 3716—3730

Long non-coding RNA MEG3 promotes fibrosis and inflammatory response in diabetic nephropathy via miR-181a/Egr-1/TLR4 axis

Fangfang Zha 1, *, , Xiaolu Qu 2, *, , Bo Tang 1, , Ji Li 1, , Yakun Wang 1, , PengXi Zheng 1, , Tingting Ji 1, , Chun Zhu 3, 4, , Shoujun Bai 1, ,

  • 1 Department of Nephrology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Qingpu District, Shanghai 201700, P.R. China
  • 2 Department of Nephrology, Shanghai Punan Hospital of Pudong New District, Pudong New District, Shanghai 200215, P.R. China
  • 3 Department of Nephrology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Chongming Branch, Chongming District, Shanghai 202150, P.R. China
  • 4 Department of Nephrology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Yangpu District, Shanghai 200092, P.R. China
* Equal contribution

received: February 17, 2019 ; accepted: June 1, 2019 ; published: June 13, 2019 ;

https://doi.org/10.18632/aging.102011
How to Cite

Copyright: Zha 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

Long non-coding RNAs (lncRNAs) play vital roles in diabetic nephropathy (DN). This research aimed to study the potential role and underlying molecular mechanisms of long non-coding RNA MEG3 in DN. We found that MEG3 was upregulated in DN in vivo and in vitro and could enhance cell fibrosis and inflammatory response in DN. MEG3 functioned as an endogenous sponge for miR-181a in mesangial cells (MCs) via direct targeting and in an Ago2-dependent manner. MiR-181a inhibition promoted MC fibrosis and inflammatory response. In addition, Egr-1 was confirmed as a target gene of miR-181a. Further investigations verified that MEG3 promotes fibrosis and inflammatory response via the miR-181a/Egr-1/TLR4 axis in vitro and in vivo. These results provide new insights into the regulation between MEG3 and the miR-181a/Egr-1/TLR4 signaling pathway during DN progression.

Abbreviations

DN: diabetic nephropathy; MCs: mesangial cells; FISH: fluorescence in situ hybridization; qRT-PCR: quantitative reverse transcription polymerase chain reaction; RIP: RNA immunoprecipitation; lncRNA: long non-coding RNA; ceRNA: competing endogenous RNA; WB: Western blot.