AMPK activation alleviated DSS-induced colitis by inhibiting ferroptosis

Objective: Ferroptosis is a newly discovered cell death mode that has been confirmed to occur in ulcerative colitis (UC) intestinal epithelial cells. Therefore, it is particularly important to find key targets to block Ferroptosis.

Methods: Human colon samples and animal models were used in this study. The Ferroptosis related protein in human colon tissue was detected by immunohistochemistry. The clinical symptoms, iron abundance and lipid peroxidation level of experimental mice were measured to evaluate the role of AMPK activation in reversing Ferroptosis.

Results: We verified the expression difference of ferroptosis-related genes and proteins between UC patients and healthy people. Besides, we also confirmed the occurrence of colonic Ferroptosis in a DSS-induced mouse model. Activation of AMPK inhibits Ferroptosis in the colon, improves symptoms and prolongs lifespan in DSS-induced colitis mice.

Conclusion: Collectively, our results illustrated that AMPK may be an important target for the inhibition of Ferroptosis, which provides a potential therapeutic strategy for colitis.

AMPK; Dextran sulfate sodium; Ferroptosis; Metformin; Ulcerative colitis.