Conclusions
Ferroptosis can be observed in colonic tissues in UC. AMPK activation inhibits ferroptosis in murine colitis model, which may act as a potential target for the treatment of colitis.
Methods
Gene expression profiles of colonic mucosa (GSE87473) were downloaded. Both human colonic samples and dextran sodium sulfate (DSS)-induced colitis murine model were used. The molecular markers of ferroptosis were detected using western blot and immunohistochemistry. Symptoms, iron abundance, and lipid peroxidation level of the mouse model were measured to evaluate the role of AMPK activation in ferroptosis.
Results
Both gene and protein expressions of GPX4 and FTH1 were decreased in UC patients compared with the healthy controls. An increased iron abundance and lipid peroxidation level in colon tissues and damaged mitochondria were found in DSS-induced colitis. AMPK expression was decreased in UC patients and correlated with FTH1 and GPX4. Activation of AMPK with metformin inhibited ferroptosis in the colon, improved symptoms, and prolonged the lifespan in DSS-induced colitis mice. Conclusions: Ferroptosis can be observed in colonic tissues in UC. AMPK activation inhibits ferroptosis in murine colitis model, which may act as a potential target for the treatment of colitis.