The function of miR-199a-5p/Klotho regulating TLR4/NF-κB p65/NGAL pathways in rat mesangial cells cultured with high glucose and the mechanism.

Abstract

Anti-aging protein Klotho may confer a renal protective effect via attenuating the nuclear factor-κB (NF-κB) p65 pathways activity. Besides, miR-199a-5p can promote gastric cancer by inhibition of Klotho protein expression. But little is known regarding to the role of miR-199a-5p/Klotho in regulating NF-κB p65 pathways in the pathogenesis of diabetic kidney disease (DKD). Thus, we explored Klotho and miR-199a-5p in terms of Toll-like receptor-4 (TLR4)/NF-κB p65/neutrophil gelatinase associated lipocalin (NGAL) signaling pathways in high glucose cultured mesangial cells (MCs). We found that high glucose increased miR-199a-5p expression, accompanied by the significantly decreased Klotho expression at both mRNA and protein. High glucose also activated TLR4/NF-κB p65/NGAL signaling pathways and promoted the downstream fibrosis and inflammatory reaction. Additionally, inhibition of miR-199a-5p or exogenous addition of Klotho restrained the activity of TLR4/NF-κB p65/NGAL signaling pathways, which in turn suppressed the inflammation and fibrosis in high glucose cultured MCs. This study provides a new basis to elucidate the protection mechanism of anti-aging protein Klotho in diabetic kidney. For the first time, our study prompts that miR-199a-5p can be used as a new therapeutic targets for DKD.

• Authors: Can Wu, Chuan Lv, Fenqin Chen, Xiaoyu Ma, Ying Shao, Qiuyue Wang
• Journal: Molecular and cellular endocrinology (Mol Cell Endocrinol) Vol. 417 Pg. 84-93 (Dec 05 2015) ISSN: 1872-8057 [Electronic] Ireland
• PMID: 26419931 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• MIRN199 microRNA, rat
• MicroRNAs
• NF-kappa B
• Tlr4 protein, rat
• Toll-Like Receptor 4
• Glucuronidase
• Klotho Proteins
• Glucose

Topics

• Animals
• Cells, Cultured
• Gene Expression Regulation
• Glucose (metabolism)
• Glucuronidase (genetics, metabolism)
• Klotho Proteins
• Mesangial Cells (drug effects, metabolism)
• MicroRNAs (genetics, metabolism)
• NF-kappa B (metabolism)
• Rats
• Signal Transduction
• Toll-Like Receptor 4 (metabolism)
• Up-Regulation