title: miR-184 and miR-150 promote renal glomerular mesangial cell aging by targeting Rab1a and Rab31.
abstract: The molecular mechanism of kidney aging is not well understood, but the abnormal expression of miRNAs with aging is considered to be an important contributor. miR-184 and miR-150 were screened using a miRNA microarray and qRT-PCR and found to be significantly upregulated in 24-month-old rats. Rat renal primary glomerular mesangial cells (GMCs) were isolated from 3-month and 24-month-old rats for the in vitro analysis of the roles of miR-184 and miR-150 in kidney aging. Bioinformatics analyses suggested that Rab1a and Rab31, which are associated with cell autophagy, were targeted by both miR-184 and miR-150. miR-184 and miR-150 were increased significantly in aging GMCs versus young cells, while Rab1a and Rab31 were significantly lower in aging cells. Furthermore, dual luciferase reporter assays revealed that miR-184 and miR-150 bound to the 3'-UTR of Rab1a and Rab31 mRNAs. Transfection of miR-184 and miR-150 mimics into young GMCs suppressed the expression of Rab1a and Rab31. Transfected cells showed lower autophagy activities and higher levels of cellular oxidative products, leading to the aging of young GMCs. However, miR-184 and miR-150 inhibitors promoted autophagy and reduced oxidative damage by upregulating Rab1a and Rab31 in old GMCs. In conclusion, miR-184 and miR-150 inhibited autophagy, promoting GMC aging.
authors.affiliation: Department of Nephrology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital and Medical College, Beijing 100853, China; Department of Nephrology, 94 Hospital of Chinese PLA, Nanchang, Jiangxi, 330002, China.
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Nephrology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital and Medical College, Beijing 100853, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Fu
authors.affiliation: Department of Nephrology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital and Medical College, Beijing 100853, China.
authors.forename: Dapeng
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Nephrology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital and Medical College, Beijing 100853, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Hong
authors.affiliation: Department of Nephrology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital and Medical College, Beijing 100853, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cui
authors.affiliation: Department of Nephrology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital and Medical College, Beijing 100853, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Nephrology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital and Medical College, Beijing 100853, China. Electronic address: xueyuan_bai@163.com.
authors.forename: Xueyuan
authors.initials: X
authors.lastname: Bai
authors.affiliation: Department of Nephrology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital and Medical College, Beijing 100853, China. Electronic address: xiangmeichen301@163.com.
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Chen
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001343:Autophagy / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics; D016922:Cellular Senescence / Q000235:genetics*; D008297:Male; D050527:Mesangial Cells / Q000502:physiology*; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D018384:Oxidative Stress / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D020691:rab GTP-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D020761:rab1 GTP-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; C551974:MIRN150 microRNA, rat; C000602309:MIRN184 microRNA, rat; D035683:MicroRNAs; C484189:Rab31 protein, rat; D020691:rab GTP-Binding Proteins; D020761:rab1 GTP-Binding Proteins
keywords: Autophagy; Glomerular mesangial cell; Oxidative stress; Renal aging; miR-150; miR-184