The STING antagonist SN-011 ameliorates cisplatin induced acute kidney injury via suppression of STING/NF-κB-mediated inflammation.

Abstract

Acute kidney injury (AKI) is a critical clinical syndrome associated with both innate and adaptive immune responses and thus increases mortality. Nevertheless, specific therapeutics for AKI are scarce so far. Recent studies have revealed that knockout of STING alleviate AKI, suggesting that STING could be an attractive target for AKI therapy. SN-011, a promising STING inhibitor, has not been reported in studies of its anti-AKI activity. In this study, we sought to examine the effects of SN-011 on AKI and explore its underlying mechanism. Our findings indicate that SN-011 could modulate the NF-κB and MAPK pathways, suppress the expression of inflammatory factors, and decrease ROS release in the cisplatin-induced cell model. In addition, SN-011 blocked the nuclear translocation of NF-κB p65, further mitigating the inflammatory response. In vivo, SN-011 enhanced survival rates and alleviated renal dysfunction. According to gene set enrichment analysis of sequencing data from mouse kidneys, we further confirm that SN-011 modulates the NF-κB and MAPK pathways. Our study suggests that SN-011 could be an attractive anti-inflammatory agent for further anti-AKI research.