STING deficiency protects against wasp venom-induced acute kidney injury

ObjectiveRecent evidence suggests a key role of the inflammatory responses in wasp venom-induced acute kidney injury (AKI). However, the potential regulatory mechanisms underlying the inflammatory responses in wasp venom-induced AKI remain unclear. STING reportedly plays a critical role in other AKI types and is associated with inflammatory responses and diseases. We aimed to investigate the involvement of STING in inflammatory responses associated with wasp venom-induced AKI.MethodsThe role of the STING signaling pathway in wasp venom-induced AKI was studied in vivo using a mouse model of wasp venom-induced AKI with STING knockout or pharmacological inhibition and in vitro using human HK2 cells with STING knockdown.ResultsSTING deficiency or pharmacological inhibition markedly ameliorated renal dysfunction, inflammatory responses, necroptosis, and apoptosis in wasp venom-induced AKI in mice. Moreover, STING knockdown in cultured HK2 cells attenuated the inflammatory response, necroptosis, and apoptosis induced by myoglobin, the major pathogenic factor in wasp venom-induced AKI. Urinary mitochondrial DNA upregulation has also been observed in patients with wasp venom-induced AKI.ConclusionsSTING activation mediates the inflammatory response in wasp venom-induced AKI. This may offer a potential therapeutic target for the management of wasp venom-induced AKI.

Automated summary

The STING signaling pathway plays a critical role in the inflammatory responses associated with wasp venom-induced acute kidney injury (AKI), as evidenced by in vivo and in vitro studies. Inhibition of this pathway could be a potential therapeutic target for managing wasp venom-induced AKI.