SENP1 protects cisplatin-induced AKI by attenuating apoptosis through regulation of HIF-1α.

Ling Wang, Xiang Gao, Xiaojing Tang, Jing Xu, Jie Zhou, Lin Li, Yun Zou, Ming Wu, Lin Xu, Pinglan Lin, Dongsheng Yao, Qing Wu, Yuan Zhou, Chaoyang Ye, Dongping Chen

Experimental cell research 2022 Oct 01

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Acute kidney injury is a clinical syndrome with both high morbidity and mortality. However, the underlying molecular mechanism of AKI is still largely unknown. The role of SENP1 in AKI is unclear, while one of its substrates, HIF-1α possesses nephroprotective effect in AKI. Herein, this study aimed to reveal the role of SENP1/HIF-1α axis in AKI by using both cell and animal models. We investigated the effects of AKI on SENP1 expression using clinical samples, and cisplatin-induced AKI model based on mice or HK-2 cells. The influence of SENP1 knockdown or over-expression on cisplatin-induced AKI was studied in vitro and in vivo. Following the exploration of the change in HIF-1α expression brought by AKI, the synergistic effects of SENP1 knockdown and HIF-1α over-expression on AKI were examined. The results showed the up-regulation of SENP1 in clinical specimens, as well as cell and animal models. The knockdown or over-expression of SENP1 in HK-2 cells could promote or inhibit AKI through regulating cell apoptosis, respectively. Moreover, SENP1+/- mice suffered from much more serious AKI compared with mice in wild type group. Furthermore, we found that HIF-1α over-expression could attenuate the promoted cell apoptosis as well as AKI induced by SENP1 knockdown. we showed that SENP1 provided protection for kidney in AKI via regulating cell apoptosis and through the regulation of HIF-1α. This study could benefit for the understanding of the pathogenesis of AKI and provide potential therapeutic target for AKI treatment. Copyright © 2022. Published by Elsevier Inc.

Citation

Ling Wang, Xiang Gao, Xiaojing Tang, Jing Xu, Jie Zhou, Lin Li, Yun Zou, Ming Wu, Lin Xu, Pinglan Lin, Dongsheng Yao, Qing Wu, Yuan Zhou, Chaoyang Ye, Dongping Chen. SENP1 protects cisplatin-induced AKI by attenuating apoptosis through regulation of HIF-1α. Experimental cell research. 2022 Oct 01;419(1):113281