mtDNA regulates cGAS-STING signaling pathway in adenomyosis

Kun Wang, Yi Wen, Xianyun Fu, Shaobin Wei, Shidan Liu, Minmin Chen
Free radical biology & medicine · 2024 · vol. 216 , pp. 80–88 · doi:10.1016/j.freeradbiomed.2024.03.012 · PMID:38494142 · W4392872108
article OA: closed CC0 ⤵ 3 in-corpus citations
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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

This study found that increased mitochondrial DNA release and cGAS-STING pathway activation contribute to hypoxia-induced endometrial stromal cell proliferation, migration, and inflammation in adenomyosis.

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Abstract

In various hyperproliferative disorders, damaged mitochondria can release mitochondrial DNA (mtDNA) into the cytoplasm, activating the cGAS-STING signaling pathway and subsequent immune imbalances. Our previous research has demonstrated that hypoxia plays a role in the development of adenomyosis (AM) by inducing mitochondrial dysfunction. However, the precise involvement of the cGAS-STING signaling pathway and mtDNA in AM remains unclear. Therefore, this study aims to investigate the relationship between mtDNA secretion, changes in the cGAS-STING signaling pathway, and the abnormal cellular proliferation observed in AM. We found the cGAS, STING, TBK1, p-TBK1, IRF3, and p-IRF3 proteins levels were significantly elevated in the tissues of patients with AM compared to the control group. Additionally, there was an increase in the expression of the pro-inflammatory cytokines IL-6 and IFN-α in the AM tissues. Hypoxia-induced an increase in the proliferation and migration abilities of endometrial stromal cells (ESCs), accompanied by the activation of the cGAS-STING signaling pathway and elevated levels of IFN-α. Furthermore, hypoxia promoted the leakage of mtDNA into the cytoplasm in AM ESCs, and the deletion of mtDNA reduced the activation of the cGAS-STING pathway. Moreover, knockdown of the STING gene inhibited the expression of TBK1, p-TBK1, IRF3, and p-IRF3 and suppressed the secretion of the inflammatory cytokines IL-6 and IFN-α. Furthermore, the migration and invasion abilities of AM ESCs were significantly diminished after STING knockdown. These findings provide valuable insights into the role of mtDNA release and the cGAS-STING signaling pathway in the pathogenesis of AM.

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Condition tags

adenomyosis

MeSH descriptors

Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis DNA, Mitochondrial DNA, Mitochondrial DNA, Mitochondrial DNA, Mitochondrial DNA, Mitochondrial DNA, Mitochondrial Cytokines Cytokines Cytokines Cytokines Cytokines Female Female Female

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