STING deficiency protects against wasp venom-induced acute kidney injury.

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.

• Authors: Ying Lv, Li Lu, Fanglin Yu, Zhao Gao, Hai Yuan, Fengqi Hu
• Journal: Inflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 72 Issue 7 Pg. 1427-1440 (Jul 2023) ISSN: 1420-908X [Electronic] Switzerland
• PMID: 37326694 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

Chemical References

• Wasp Venoms

Topics

• Humans
• Wasp Venoms (metabolism)
• Acute Kidney Injury (chemically induced, prevention & control, metabolism)
• Mitochondria (metabolism)
• Apoptosis
• Kidney (pathology)