Estrogen-related receptor (ERR) γ protects against puromycin aminonucleoside-induced podocyte apoptosis by targeting PI3K/Akt signaling. (September 2016)

• Record Type: Journal Article
• Authors: Gong, Wei; Yu, Jing; Wang, Qilei; Li, Shuzhen; Song, Jiayu; Jia, Zhanjun; Huang, Songming; Zhang, Aihua
• Is Part Of: International journal of biochemistry & cell biology. Volume 78(2016:Sep.)
• Page Start: 75
• Page End: 86
• Publication Date: 2016-09
• Subjects: ERR estrogen related receptor -- GBM glomerular basement membrane -- PAN puromycin aminonucleoside -- Bcl-2 B-cell lymphoma 2 -- BAX Bcl-2-associated X protein -- B7-1 also termed as CD80 cluster of differentiation 80 -- PI3K phosphatidylinositol-4, 5-bisphosphate 3-kinase -- Akt also termed as PKB protein kinase B -- qRT-PCR quantitative real time PCR; Podocyte -- ERRγ -- Apoptosis -- PI3K/Akt; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2016.07.005
• Languages: English
• ISSNs: 1357-2725

Abstract

Abstract: Accumulating evidence has shown that podocyte apoptosis is of vital importance for the development of glomerulosclerosis and progressive loss of renal function. However, the molecular mechanisms leading to podocyte apoptosis are still elusive. In this study, we investigated the role of estrogen-related receptor (ERR) γ in podocyte apoptosis, as well as the underlying mechanisms. Treatment of PAN caused a dose- and time-dependent podocyte apoptosis in line with a significant downregulation of ERRγ. Interestingly, the occurrence of ERRγ downregulation appeared earlier than the onset of cell apoptosis, suggesting a potential that ERRγ reduction triggered apoptotic response in podocyte. To test this hypothesis, ERRγ siRNA was administered to the podocytes. Strikingly, ERRγ silencing resulted in a significant cell apoptosis accompanied with increased injury markers of B7-1 and cathepsin L and decreased podocyte protein nephrin. In contrast, overexpression of ERRγ remarkably attenuated PAN-induced cell apoptosis. Moreover, ERRγ overexpression stimulated PI3K/Akt signaling pathway evidenced by increased expression of PI3K subunits p85α and p110α and phosphorylated Akt. Importantly, a specific PI3K inhibitor LY294002 entirely reversed the anti-apoptotic effect of ERRγ following PAN treatment. Finally, we observed a striking downregulation of ERRγ in PAN-treated rat kidneys, suggesting that our cell model replicated the in vivo condition. Taken together, these data highly suggested that ERRγ played a novel role in modulating podocyte apoptosis by targeting PI3K/Akt signaling pathway.