Intestinal Epithelial Cell Ferroptosis in Ulcerative Colitis: Pathogenesis, Signaling Networks, and Therapeutic Implications

Abstract

The ferroptosis of intestinal epithelial cells (IECs), an iron-dependent form of cell death driven by lipid peroxidation, has emerged as a critical pathogenic driver of ulcerative colitis (UC). This review summarizes the core hallmarks of IEC ferroptosis in UC—specifically, lipid peroxidation, iron overload, and antioxidant system dysregulation—and describes key regulatory signaling networks, including the Nrf2/HO-1, SLC7A11/GPX4, and AMPK/mTOR pathways. Furthermore, we systematically evaluated emerging therapeutic strategies targeting these mechanisms, categorized into antioxidant activation, iron and lipid metabolism regulation, immune and microbiota modulation, and multitarget interventions. Elucidating this complex ferroptotic regulatory network provides a vital theoretical foundation for the development of novel disease-stage-specific therapeutic paradigms for UC management.

Keywords

Ferroptosis / Ulcerative colitis / Intestinal epithelial cells / Therapeutic strategies / Lipid peroxidation / Iron overload / Antioxidant system dysregulation

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Funding

National Natural Science Foundation of China(82305199)

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