title: 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.affiliation: Department of Endocrinology, The First Hospital Affiliated to China Medical University, Shenyang, Liaoning, China.
authors.forename: Can
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Endocrinology, People's Hospital of Liaoning Province, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Lv
authors.affiliation: Cadre Department, The First Hospital Affiliated to China Medical University, Shenyang, Liaoning, China.
authors.forename: Fenqin
authors.initials: F
authors.lastname: Chen
authors.affiliation: Cadre Department, The First Hospital Affiliated to China Medical University, Shenyang, Liaoning, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Endocrinology, The First Hospital Affiliated to China Medical University, Shenyang, Liaoning, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Department of Endocrinology, The First Hospital Affiliated to China Medical University, Shenyang, Liaoning, China. Electronic address: wqycmu123@163.com.
authors.forename: Qiuyue
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism*; D000090265:Klotho Proteins; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C552425:MIRN199 microRNA, rat; D035683:MicroRNAs; D016328:NF-kappa B; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D005966:Glucuronidase; D000090265:Klotho Proteins; D005947:Glucose
keywords: Anti-aging protein Klotho; Diabetic kidney disease; Neutrophil gelatinase associated lipocalin; Toll-like receptor-4; miR-199a-5p