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Early autophagy activation inhibits podocytes from apoptosis induced by aldosterone
Authors:WANG Wen?yan  DING Gui?xia  YUAN Yang?gang  ZHU Chun?hua  ZHANG Ai?hua  HUANG Song?ming
Institution:Department of Nephrology, Nanjing Children's Hospital, Nanjing Medical University, Nanjing 210008, China; Corresponding author: HUANG Song?ming, Email: smhuang@njmu.edu.cn
Abstract:Objective To explore the protection of early autophagy activation on podocyte injury induced by aldosterone. Methods In vitro cultured mouse podocyte clones (MPC5) were treated with aldosterone for 6, 12, 24, 48 h respectively. Apoptosis of podocytes was detected by Annexin V combined with flow cytometry. After 24 h treatment with aldosterone, the existence of apoptotic body and autophagosome was observed by electron microscopy. The protein expressions of LC3, caspase?3 and nephrin were examined by Western blotting. The mRNA expression of Beclin?1 was detected by real?time PCR. Results The induction of apoptosis and autophagy by aldosterone in podocytes was in time?dependent mannner. After 24 h treatment with aldosterone, the apoptosis was increased by 26.5% (P<0.05) and the expression of nephrin was decreased by 28.0% (P<0.05) compared to control group. Aldosterone remarkably induced the expression of Beclin?1 at 6 h and promoted the transformation of LC3?Ⅰto LC3?Ⅱ at 12 h (P<0.05). Compared to simple aldosterone treatment, the apoptosis rate of podocyte was increased by 39.0%(P<0.05)and the expression of nephrin was declined by 19.5%(P<0.05) after 3?methyladenine (3?MA) pre?treatment. Conclusions Aldosterone can induce autophagy and apoptosis in podocytes. Autophagy occurs earlier (12 h) than apoptosis (24 h). The occurrence of autophagy can inhibit the apoptosis,so the autophagy pathway may be a new research topic of glomerular disease treatment.
Keywords:Podocytes         Aldosterone         Apoptosis         Autophagy  
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