Citation

Lv Y, Lu L, Yu F, Gao Z, Yuan H, Hu F. J. Inflamm. Res. 2023; ePub(ePub): ePub.

Copyright

(Copyright © 2023, Birkhauser)

DOI

10.1007/s00011-023-01749-5

PMID

37326694

Abstract

OBJECTIVE: Recent 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.

METHODS: The 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.

RESULTS: STING 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.

CONCLUSIONS: STING 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.

Language: en

Keywords

Acute kidney injury; Inflammatory response; Stimulator of interferon genes; Wasp venom