Remote Ischemic Preconditioning Protects Cisplatin-Induced Acute Kidney Injury through the PTEN/AKT Signaling Pathway

Abstract

Although cisplatin (Cis) is an effective chemotherapeutic agent in treatment of various cancers, its adverse effect of nephrotoxicity limits the clinical application. Remote ischemic preconditioning (RIPC) is a strategy to induce resistance in a target organ against the oxidative stress and injury by applying transient, brief episodes of ischemia. However, whether RIPC exerts protective effect on Cis-induced renal injury remains unclear. In this study, we showed that RIPC significantly alleviated the renal functional and histopathological damage of Cis-induced acute kidney injury (AKI) mice. Furthermore, RIPC substantially reversed the downregulation of miR-144 and upregulation of PTEN in renal tissues of Cis-induced AKI mice and alleviated tubular cell apoptosis via activating PTEN/AKT signaling. In mechanism, we demonstrated that miR-144 directly targets the 3'-UTR of PTEN mRNA, and then the elevation of miR-144 in RIPC activates PTEN/AKT signaling by downregulating PTEN expression to achieve its antiapoptosis effect. Collectively, our results indicate that RIPC may be a potential therapeutic strategy in Cis-induced AKI, and provide insights on the underlying molecular mechanisms of cisplatin's nephrotoxicity.