STAT1 promotes ferroptosis and inflammation in mouse hepatic ischemia-reperfusion injury

Hepatic ischemia reperfusion injury (HIRI) is a critical complication in liver surgery and transplantation, driven by excessive inflammation and hepatocellular death. Although ferroptosis is recognized as a major form of regulated cell death in HIRI, the upstream regulators of this process remain poorly defined. Here, we show that the transcription factor STAT1 plays a pivotal role in promoting ferroptosis and inflammation during HIRI. Using male mice subjected to partial hepatic ischemia followed by reperfusion, we find that STAT1 protein is significantly upregulated in liver tissues. Genetic deletion of Stat1 markedly reduces lipid peroxidation, suppresses proinflammatory cytokine expression, and improves liver histology and function. Mechanistically, STAT1 represses miR-497-5p transcription, leading to HDAC7 activation, which together promotes ferroptosis and inflammatory responses in HIRI. These results identify STAT1 as a central link between ferroptosis and inflammation in HIRI, suggesting that targeting STAT1 may offer a novel therapeutic strategy for liver protection in clinical settings.