Long Noncoding RNA MEG3-205/Let-7a/MyD88 Axis Promotes Renal Inflammation and Fibrosis in Diabetic Nephropathy.

Abstract

Aim:

The aim of this study was to investigate the role and mechanism of long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3)-205 in renal inflammation and fibrosis in diabetic nephropathy (DN).

Materials and Methods:

lncRNA microarray profiling was used to examine differentially expressed lncRNAs of kidney tissues in db/db mice compared to db/m mice. Mouse mesangial cells (mMCs) were cultured in vitro with advanced glycation end products (AGEs) via transfection with lncRNA MEG3-205 siRNAs or plasmids. The role of lncRNA MEG3-205 in vivo was examined in db/db mice treated with long-acting lncRNA MEG3-205 siRNA. The interaction between lncRNA MEG3-205 and let-7a was investigated using luciferase assay and RNA immunoprecipitation assay.

Results:

lncRNA MEG3-205 was markedly upregulated in renal tissues of db/db mice, DN patients, and AGEs-treated mesangial cells. Overexpression of lncRNA MEG3-205 promoted the secretion of pro-inflammatory cytokines and synthesis of extracellular matrix proteins in mesangial cells. Both lncRNA MEG3-205 and myeloid differentiation primary-response protein 88 (MyD88) could bind to let-7a, and lncRNA MEG3-205 overexpression can significantly rescue the silencing effect of let-7a on MyD88 protein expression in mMCs. Mechanistically, we identified that lncRNA MEG3-205 could act as a competing endogenous RNA by binding with let-7a and thus regulate MyD88. Knockdown of lncRNA MEG3-205 alleviated albuminuria and attenuated renal inflammation and fibrosis in db/db mice.

Conclusion:

These findings indicated an important role of the lncRNA MEG3-205/let-7a/MyD88 axis in regulating renal inflammation and fibrosis in DN. Targeting lncRNA MEG3-205 might present a promising therapeutic strategy for DN.

• Authors: Qimei Luo, Xi Xia, Qingqing Luo, Yue Qiu, Lan Dong, Chen Zhao, Fenfen Peng, Jing Yu, Fengxian Huang, Feng He
• Journal: Kidney diseases (Basel, Switzerland) (Kidney Dis (Basel)) Vol. 8 Issue 3 Pg. 231-245 (May 2022) ISSN: 2296-9381 [Print] Switzerland
• PMID: 35702702 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 by S. Karger AG, Basel.