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Advances in the study of ferroptosis and endoplasmic reticulum stress in the pathological mechanisms of ulcerative colitis
Received date: 2025-10-29
Online published: 2026-02-25
Ulcerative colitis （UC） represents a specific manifestation of inflammatory bowel disease， which is distinguished by the chronic and recurrent inflammation of the colonic mucosa. The pathogenesis of UC encompasses the disruption of the intestinal mucosal barrier， the dysregulation of immune homeostasis， and the activation of multiple stress-related cell death pathways. In recent years， mounting evidence has demonstrated that ferroptosis， a type of regulated cell death propelled by iron-dependent lipid peroxidation， and endoplasmic reticulum stress （ERS）， mainly mediated by the unfolded protein response （UPR）， assume crucial roles in the onset and progression of UC. Research has revealed that colonic tissues obtained from patients with UC and experimental colitis models display dysregulated iron homeostasis， the accumulation of lipid peroxides， the depletion of glutathione （GSH）， and the inactivation of glutathione peroxidase 4 （GPX4）， all of which are characteristic hallmarks of ferroptosis. It has been reported that pharmacological or genetic inhibition of ferroptosis can mitigate mucosal injury and inflammatory responses. Meanwhile， the persistent activation of ERS in intestinal epithelial cells is evident， as indicated by the functional exhaustion of the endoplasmic reticulum chaperone glucose - regulated protein 78 （GRP78） and the enhanced signaling of C/EBP homologous protein （CHOP） and X-box binding protein 1 （XBP1）. Dysregulated ERS can directly lead to goblet cell loss and the impairment of epithelial barrier function. Significantly， ferroptosis and ERS are not independent processes but interact with each other within the inflammatory microenvironment of UC. ERS can enhance cellular susceptibility to ferroptosis by depleting GSH and intensifying oxidative stress. Conversely， excessive lipid peroxides and damage-associated molecular patterns produced during ferroptosis may further exacerbate ERS， thus forming a detrimental feedback loop. Therefore， therapeutic strategies targeting the ferroptosis-ERS axis， especially those integrated with nanotechnology-based delivery systems for precise regulation， might represent a promising approach for the treatment of UC.
Key words： ulcerative colitis; ferroptosis; endoplasmic reticulum stress
Qianjun XIAO , Chunhui CUI . Advances in the study of ferroptosis and endoplasmic reticulum stress in the pathological mechanisms of ulcerative colitis[J]. The Journal of Practical Medicine, 2026 , 42(4) : 714 -722 . DOI: 10.3969/j.issn.1006-5725.2026.04.024
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