title: MicroRNA-30e targets BNIP3L to protect against aldosterone-induced podocyte apoptosis and mitochondrial dysfunction.
abstract: MicroRNAs are essential for the maintenance of podocyte homeostasis. Emerging evidence has demonstrated a protective role of microRNA-30a (miR-30a), a member of the miR-30 family, in podocyte injury. However, the roles of other miR-30 family members in podocyte injury are unclear. The present study was undertaken to investigate the contribution of miR-30e to the pathogenesis of podocyte injury induced by aldosterone (Aldo), as well as the underlying mechanism. After Aldo treatment, miR-30e was reduced in a dose-and time-dependent manner. Notably, overexpression of miR-30e markedly attenuated Aldo-induced apoptosis in podocytes. In agreement with this finding, miR-30e silencing led to significant podocyte apoptosis. Mitochondrial dysfunction (MtD) has been shown to be an early event in Aldo-induced podocyte injury. Here we found that overexpression of miR-30e improved Aldo-induced MtD while miR-30e silencing resulted in MtD. Next, we found that miR-30e could directly target the BCL2/adenovirus E1B-interacting protein 3-like (BNIP3L) gene. Aldo markedly enhanced BNIP3L expression in podocytes, and silencing of BNIP3L largely abolished Aldo-induced MtD and cell apoptosis. On the contrary, overexpression of BNIP3L induced MtD and apoptosis in podocytes. Together, these findings demonstrate that miR-30e protects mitochondria and podocytes from Aldo challenge by targeting BNIP3L.
authors.affiliation: Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, China; and.|Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, China; and.|Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Deng
authors.affiliation: Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, China; and.|Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, China; and.|Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, China; and.|Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Ni
authors.affiliation: Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, China; and.|Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, China; and.|Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China.
authors.forename: Jiajuan
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, China; and.|Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China.
authors.forename: Mi
authors.initials: M
authors.lastname: Bai
authors.affiliation: Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, China; and.|Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China.
authors.forename: Zhanjun
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, China; and.|Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China.
authors.forename: Songming
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, China; and zhaihua@njmu.edu.cn.|Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Zhang
mesh_terms: D000450:Aldosterone / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
chemical_list: D008565:Membrane Proteins; D035683:MicroRNAs; C534715:Mirn30d microRNA, mouse; D024101:Mitochondrial Proteins; C501741:Nix protein, mouse; D000450:Aldosterone
keywords: BNIP3L; apoptosis; miR-30e; mitochondrial dysfunction; podocytes