title: PGC-1α overexpression protects against aldosterone-induced podocyte depletion: role of mitochondria.
abstract: Growing evidence has shown that podocyte number is a critical determinant for the development of glomerulosclerosis and progressive renal failure. We previously reported that mitochondrial dysfunction (MtD) is an early event in podocyte injury. Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is an important modulator of mitochondrial biogenesis. Here, we investigated the role of PGC-1α overexpression in podocyte depletion and the involvement of mitochondria in this process. Following chronic aldosterone (Aldo) infusion for 14 days, we observed a remarkable podocyte loss, podocyte phenotypic changes, and albuminuria in WT mice. However, all these abnormalities were significantly attenuated in PGC-1α transgenic mice. Next, we examined mitochondrial function in both genotypes with or without Aldo infusion. As expected, Aldo-induced MtD in glomeruli was markedly improved in PGC-1α transgenic mice. In vitro, Aldo induced podocyte detachment and phenotypic changes in line with MtD in dose- and time-dependent manners. Similarly, ethidium bromide, an inducer of MtD, mimicked Aldo effects on podocyte detachment and phenotypic alterations. Notably, overexpression of PGC-1α in podocytes entirely reversed Aldo-induced podocyte detachment, phenotypic changes, and MtD. Taken together, these findings demonstrate that PGC-1α protects against podocyte depletion and phenotypic changes possibly by maintaining normal mitochondrial function.
authors.affiliation: Department of Nephrology, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, China.|Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Yanggang
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Nephrology, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, China.|Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China.
authors.forename: Mi
authors.initials: M
authors.lastname: Bai
authors.affiliation: Department of Nephrology, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, China.|Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China.
authors.forename: Guixia
authors.initials: G
authors.lastname: Ding
authors.affiliation: Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China.
authors.forename: Zhanjun
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Department of Nephrology, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, China.|Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China.
authors.forename: Songming
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Nephrology, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, China.|Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Zhang
mesh_terms: D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D007674:Kidney Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000096:biosynthesis* / Q000235:genetics; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology
chemical_list: D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D000450:Aldosterone
keywords: PGC-1α; Pathology Section; aldosterone; mitochondria; podocyte loss; podocytes