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

Background: 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-1 alpha possesses nephroprotective effect in AKI. Herein, this study aimed to reveal the role of SENP1/HIF-1 alpha axis in AKI by using both cell and animal models. Methods: 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-1 alpha expression brought by AKI, the synergistic effects of SENP1 knockdown and HIF-1 alpha over-expression on AKI were examined. Results: 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-1 alpha over-expression could attenuate the promoted cell apoptosis as well as AKI induced by SENP1 knockdown. Conclusions: we showed that SENP1 provided protection for kidney in AKI via regulating cell apoptosis and through the regulation of HIF-1 alpha. This study could benefit for the understanding of the pathogenesis of AKI and provide potential therapeutic target for AKI treatment.

Automated summary

This study reveals the role of SENP1 in acute kidney injury (AKI) and demonstrates that it provides kidney protection through regulating cell apoptosis and HIF-1 alpha expression. This finding is important for understanding the pathogenesis of AKI and identifying potential therapeutic targets for its treatment.