TFAM Deficiency Triggers mtDNA Leakage and cGAS-STING-Mediated Intestinal Ischemia-Reperfusion Injury.

ABSTRACT: Intestinal Ischemia-Reperfusion (IIR) injury is a common clinical pathophysiological condition, yet the complex molecular mechanisms underlying its pathology remain incompletely understood. This study aims to explore the precise molecular mechanisms of IIR injury, with a focus on the role of the cGAS-STING signaling pathway. Using a mouse IIR model and hypoxia/reoxygenation (HR) model in HT-29 cells and small intestinal organoids, we observed that IIR significantly induces oxidative stress and activates the cGAS-STING pathway, which is associated with exacerbated small intestinal tissue damage and enhanced inflammatory responses. Further investigation revealed that mitochondrial DNA (mtDNA) leakage is a critical trigger for the activation of the cGAS-STING pathway. The introduction of exog

SUBMITTER: Ding K 

PROVIDER: S-EPMC12722360 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature