Effects of p53 on aldosterone-induced mesangial cell apoptosis in vivo and in vitro.
Aldosterone (ALD) is a well‑known hormone, which may initiate renal injury by inducing mesangial cell (MC) injury in chronic kidney disease (CKD); however, the molecular mechanism remains unknown. The aim of the present study was to investigate the effects of p53 on ALD‑induced MC apoptosis and elucidate the underlying molecular mechanism. For the in vivo studies, rats were randomly assigned to receive normal saline or ALD for 4 weeks. The ratio of MC apoptosis was analysed by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay. In addition, the expression level and localisation of p53, a well-known cell apoptosis-associated key protein, were detected by immunofluorescence. For the in vitro studies, rat MCs were incubated in medium containing either buffer (control) or ALD (10‑6 M) for 24 h. The cell apoptosis ratio was assessed by flow cytometry, and the expression level of p53 was assessed by reverse transcription quantitative polymerase chain reaction and western blotting. In order to confirm the role of p53 in ALD‑regulated cell apoptosis, a rescue experiment was performed using targeted small interfering (si)RNA to downregulate the expression of p53. The ALD‑treated rats exhibited greater numbers of TUNEL‑positive MCs and higher expression levels of p53 when compared with the control group. Furthermore, the ratio of MC apoptosis and the p53 expression level were significantly increased following ALD exposure, compared with the control group. Additionally, in the rescue experiment, the effects of ALD on MC were blocked by downregulating the expression level of p53 in MCs. The present study hypothesized that ALD may directly contribute to the occurrence of MC apoptosis via p53, which may participate in ALD-induced renal injury.
Department of Pediatric Nephrology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, P.R. China.
Huimin
H
Shi
Department of Pediatric Nephrology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, P.R. China.
Aiqing
A
Zhang
Department of Pediatric Nephrology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, P.R. China.
Yanfang
Y
He
Department of Nephrology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 200040, P.R. China.
Min
M
Yang
Department of Pediatric Nephrology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, P.R. China.
Weihua
W
Gan
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D015415:Biomarkers; D015870:Gene Expression; D007677:Kidney Function Tests; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D015415:Biomarkers; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D000450:Aldosterone