Promotive role of IRF7 in ferroptosis of colonic epithelial cells in ulcerative colitis by the miR-375-3p/SLC11A2 axis

Ferroptosis is implicated within the advancement of ulcerative colitis (UC), and interferon regulatory factor 7 (IRF7) plays a role in cell dying. This research probed the mechanism of IRF7 in ferroptosis of colonic epithelial cells (ECs) in rodents with dextran sodium sulfate (DSS)-caused UC. The UC mouse model and also the in vitro ferroptosis model were correspondingly established by DSS feeding and also the treatment with FIN56 (a ferroptosis inducer). Outcomes of quantitative real-time polymerase squence of events and western blotting revealed the upregulation of IRF7 and solute carrier family 11 member 2 (SLC11A2/NRAMP2/DMT1) and also the downregulation of microRNA (miR)-375-3p in DSS-treated rodents and FIN56-treated ECs. Silencing of IRF7 improved the signs and symptoms of UC in DSS-caused rodents and decreased the amount of tumor necrosis factor a, interleukin 6, monocyte chemoattractant protein 1, and interleukin 1ß, reactive oxygen species, iron ions, fat peroxidation, and elevated glutathione and glutathione peroxidase 4. Chromatin immunoprecipitation and dual-luciferase assays demonstrated that binding of IRF7 towards the miR-375-3p promoter inhibited miR-375-3p expression, and miR-375-3p covered up SLC11A2 transcription. The save experiments says knockdown of miR-375-3p neutralized the function of silencing IRF7 in alleviating ferroptosis of colonic ECs. Overall, IRF7 upregulated SLC11A2 transcription by inhibiting miR-375-3p expression, therefore prompting ferroptosis of colonic ECs and UC progression in DSS-treated rodents.