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Manganese Exacerbates ConA-Induced Liver Inflammation via the cGAS-STING Signaling Pathway

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Abstract

There is a potential association between the dysregulation of trace elements and impaired liver function. Elevated levels of manganese, an essential metal ion, have been observed in liver-related diseases, and excessive intake of manganese can worsen liver damage. However, the specific mechanisms underlying manganese-induced liver injury are not well understood. The aim of our study was to investigate the effects of excess manganese on autoimmune hepatitis (AIH) and elucidate its mechanisms. Our findings revealed that manganese exacerbates liver damage under ConA-induced inflammatory conditions. Transcriptomic and experimental data suggested that manganese enhances inflammatory signaling and contributes to the inflammatory microenvironment in the liver of AIH mice. Further investigations demonstrated that manganese exacerbates liver injury by activating the cGAS-STING signaling pathway and its downstream pro-inflammatory factors such as IFN\(\alpha\), IFN\(\beta\), TNF\(\alpha\), and IL-6 in the liver of AIH mice. These results suggest that manganese overload promotes the progression of AIH by activating cGAS-STING-mediated inflammation, providing a new perspective for the treatment and prognosis of AIH.

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DATA AVAILABILITY

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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ACKNOWLEDGEMENTS

The authors thank Putuo People’s Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.

Funding

This work was supported by grants from the National Natural Science Foundation of China (32270754 and 32070768).

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Authors and Affiliations

  1. Putuo People’s Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China

    Kaidireya Saimaier, Sanxing Han, Jie Lv, Wei Zhuang, Ling Xie, Guangyu Liu, Chun Wang, Ru Zhang, Qiuhong Hua, Changjie Shi & Changsheng Du

  2. Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China

    Wei Zhuang

  3. College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China

    Wei Zhuang

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  1. Kaidireya Saimaier
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  11. Changsheng Du
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Contributions

All authors participated in the study and supported the publication of the final version. (I) Design and experimentation: Kaidireya Saimaier, Sanxing Han, Ling Xie, Chun Wang, Jie Lv, Wei Zhuang Guangyu Liu, Ru Zhang, Qiuhong Hua, and Changjie Shi; (II) supervision: Changsheng Du; (III) manuscript writing: Kaidireya Saimaier and Changsheng Du.

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Correspondence to Changsheng Du.

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Saimaier, K., Han, S., Lv, J. et al. Manganese Exacerbates ConA-Induced Liver Inflammation via the cGAS-STING Signaling Pathway. Inflammation 47, 333–345 (2024). https://doi.org/10.1007/s10753-023-01912-4

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