Inhibition of PTEN activity aggravates cisplatin-induced acute kidney injury
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Jun Zhou1, Youling Fan2, Simin Tang1, Huiping Wu1, Jiying Zhong1, Zhengxing Huang1, Chengxiang Yang1 and Hongtao Chen3
1Department of Anesthesiology, The First People’s Hospital of Foshan, Foshan, Guangdong Province, 528000, China
2Department of Anesthesiology, Panyu Central Hospital, Guangzhou, Guangdong Province, 511400, China
3Department of Anesthesiology, Eighth People’s Hospital of Guangzhou, Guangzhou, Guangdong Province, 510060, China
Hongtao Chen, email: [email protected]
Keywords: acute kidney injury, PTEN, inflammatory cytokines, apoptosis, p53
Received: March 13, 2017 Accepted: July 18, 2017 Published: September 08, 2017
Cisplatin (cis-Diamminedichloroplatinum II) has been widely and effectively used in chemotherapy against tumors. Nephrotoxicity due to cisplatin is one of the most common clinical causes of acute kidney injury (AKI), which has a poor prognosis and high mortality. The signaling mechanisms underlying cisplatin-induced AKI are not completely understood. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor that negatively regulates the cell-survival pathway and is considered a double-edged sword in organ damage. In this study, we examined the effect that inhibiting PTEN activity in experimental models of cisplatin-induced AKI had on the degrees of AKI. Compared with vehicle mice, mice treated with bpV(pic) (specific inhibitor of PTEN) had exacerbated renal damage due to cisplatin-induced AKI. Furthermore, inhibition of PTEN activity increased cell apoptosis in the kidneys of mice induced by cisplatin. More inflammatory cytokines were activated after cisplatin treatment in mice of the bpV(pic)-treated group compared with vehicle mice, and these inflammatory cytokines may be partially derived from bone marrow cells. In addition, inhibiting PTEN activity decreased the phosphorylation of p53 in the pathogenesis of cisplatin-induced AKI. In summary, our study has demonstrated that inhibiting PTEN activity aggravates cisplatin-induced AKI via apoptosis, inflammatory reaction, and p53 signaling pathway. These results indicated that PTEN may serve as a novel therapeutic target for cisplatin-induced AKI.
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