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STING deficiency protects against wasp venom-induced acute kidney injury

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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.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding authors on reasonable request.

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Funding

This study was supported by grants from the Natural Science Foundation, Hubei Province, China (2022CFD108).

Author information

Author notes

  1. Ying Lv and Li Lu contributed equally to this work.

Authors and Affiliations

  1. School of Medicine, Wuhan University of Science and Technology, Wuhan, 430065, China

    Ying Lv

  2. Department of Nephrology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, 441000, China

    Ying Lv, Li Lu, Fanglin Yu, Zhao Gao, Hai Yuan & Fengqi Hu

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  1. Ying Lv
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  6. Fengqi Hu
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Contributions

HY and FH designed the study. YL, LL, and FY conducted the experiments. YL, LL, and ZG analyzed the data and wrote the manuscript. ZG and FH contributed to the revision of the manuscript. All authors read and approved the final version of the manuscript.

Corresponding authors

Correspondence to Hai Yuan or Fengqi Hu.

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Conflict of interest

The authors declare that they have no competing interests.

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. Ethical approval was granted by the Xiangyang Central Hospital Ethics Committee.

Consent to participate

Written informed consent was obtained from all individual patients included in this study.

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Responsible Editor: Thiago Cunha.

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Cite this article

Lv, Y., Lu, L., Yu, F. et al. STING deficiency protects against wasp venom-induced acute kidney injury. Inflamm. Res. 72, 1427–1440 (2023). https://doi.org/10.1007/s00011-023-01749-5

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  • DOI: https://doi.org/10.1007/s00011-023-01749-5

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