LncRNA HOTAIR facilitates high glucose-induced mesangial cell proliferation, fibrosis and oxidative stress in diabetic nephropathy via regulating miR-147a/WNT2B axis.

Abstract

BACKGROUND:

Long non-coding RNAs (lncRNAs) have been shown to be involved in the regulation of many disease progression. However, the role of lncRNA HOX transcript antisense RNA (HOTAIR) in diabetic nephropathy (DN) remains unclear.

METHODS:

High glucose (HG)-induced human mesangial cells (HMC) was used to construct DN cell models in vitro. HMC proliferation was evaluated by CCK8 assay and EDU staining. Protein levels of proliferation markers, fibrosis markers, and wingless-type family member 2B (WNT2B) were measured using western blot analysis. HMC oxidative stress was assessed by determining the levels of oxygen species and malondialdehyde, as well as superoxide dismutase activity. Relative expression levels of lncRNA HOTAIR, microRNA (miR)-147a, and WNT2B were examined using quantitative real-time PCR. The interaction between miR-147a and lncRNA HOTAIR or WNT2B was confirmed by dual-luciferase reporter assay and RIP assay.

RESULTS:

Our data showed that lncRNA HOTAIR knockdown could inhibit the proliferation, fibrosis, and oxidative stress in HG-induced HMC. LncRNA HOTAIR could serve as a sponge of miR-147a. The inhibition effect of lncRNA HOTAIR silencing on the biological functions of HG-induced HMC could be reversed by miR-147a inhibitor. WNT2B was targeted by miR-147a, and its overexpression also overturned the suppressive effect of miR-147a on the proliferation, fibrosis, and oxidative stress of HG-induced HMC.

CONCLUSION:

In total, our research pointed out that lncRNA HOTAIR could mediate miR-147a/WNT2B axis to promote DN progression.

• Authors: Xin Wang, Wei Wang, Weizhong HuangFu, Zhonghua Liu, Feng Zhao
• Journal: Diabetology & metabolic syndrome (Diabetol Metab Syndr) Vol. 14 Issue 1 Pg. 33 (Feb 22 2022) ISSN: 1758-5996 [Print] England
• PMID: 35193668 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s).