title: miR-135 family members mediate podocyte injury through the activation of Wnt/β-catenin signaling.
abstract: The upregulation of Wnt/β-catenin signaling occurs in virtually all types of kidney disease and is associated with podocyte injury. However, the precise mechanisms involved in the development of kidney disease remain to be elucidated. MicroRNAs (miRNAs or miRs) are a class of short non-coding RNAs and they have been shown to be regulators of gene expression, mainly by binding to the untranslated region (UTR) of mRNAs. The aim of the present study was to determine the role of the 2 members of the miR-135 family (miR‑135a and miR‑135b) in podocyte injury and to elucidate the mechanisms responsible for the damage to podocytes. The results revealed that miR-135a and miR-135b were upregulated in models of podocyte injury and in glomeruli isolated from patients with focal segmental glomerulosclerosis (FSGS). The ectopic expression of miR-135a and miR‑135b led to severe podocyte injury and the disorder of the podocyte cytoskeleton. Our findings demonstrated that miR-135a and miR‑135b activated Wnt/β‑catenin signaling and induced the nuclear translocation of β-catenin. Using luciferase reporter assays, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, glycogen synthase kinase 3β (GSK3β) was identified as a target gene of miR-135a and miR‑135b. To the best of our knowledge, this is the first study to demonstrate that members of the miR-135 family (specifically miR-135a and miR‑135b) regulate the expression of GSK3β, thus playing a role in the development of podocyte injury and the disorder of the podocyte cytoskeleton. This is an important finding as it may contribute to the development of novel therapeutics for podocyte injury-associated glomerulopathies.
authors.affiliation: Division of Molecular Nephrology and Creative Training Center for Undergraduates, The M.O.E. Key Laboratory of Laboratory Medical Diagnostics, College of Laboratory Medicine, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Xianggui
authors.initials: X
authors.lastname: Yang
authors.affiliation: Division of Molecular Nephrology and Creative Training Center for Undergraduates, The M.O.E. Key Laboratory of Laboratory Medical Diagnostics, College of Laboratory Medicine, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Division of Molecular Nephrology and Creative Training Center for Undergraduates, The M.O.E. Key Laboratory of Laboratory Medical Diagnostics, College of Laboratory Medicine, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Nie
authors.affiliation: Division of Molecular Nephrology and Creative Training Center for Undergraduates, The M.O.E. Key Laboratory of Laboratory Medical Diagnostics, College of Laboratory Medicine, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Tianming
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The Fifth Medical College, Peking University, Beijing, P.R. China.
authors.forename: Xuejing
authors.initials: X
authors.lastname: Yu
authors.affiliation: Research Center of Combined Traditional Chinese and Western Medicine, The Affiliated Traditional Medicine Hospital, Luzhou Medical College, Luzhou, Sichuan, P.R. China.
authors.forename: Honglian
authors.initials: H
authors.lastname: Wang
authors.affiliation: Division of Molecular Nephrology and Creative Training Center for Undergraduates, The M.O.E. Key Laboratory of Laboratory Medical Diagnostics, College of Laboratory Medicine, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Qianyin
authors.initials: Q
authors.lastname: Li
authors.affiliation: Division of Molecular Nephrology and Creative Training Center for Undergraduates, The M.O.E. Key Laboratory of Laboratory Medical Diagnostics, College of Laboratory Medicine, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Peng
authors.affiliation: Division of Molecular Nephrology and Creative Training Center for Undergraduates, The M.O.E. Key Laboratory of Laboratory Medical Diagnostics, College of Laboratory Medicine, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Zhaomin
authors.initials: Z
authors.lastname: Mao
authors.affiliation: Division of Molecular Nephrology and Creative Training Center for Undergraduates, The M.O.E. Key Laboratory of Laboratory Medical Diagnostics, College of Laboratory Medicine, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Division of Molecular Nephrology and Creative Training Center for Undergraduates, The M.O.E. Key Laboratory of Laboratory Medical Diagnostics, College of Laboratory Medicine, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Ge
authors.initials: G
authors.lastname: Li
mesh_terms: D000818:Animals; D002460:Cell Line; D015536:Down-Regulation; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D050199:Podocytes / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation; D060449:Wnt Signaling Pathway
chemical_list: C544965:MIRN135 microRNA, human; D035683:MicroRNAs; C549289:Mirn135 microRNA, mouse; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3