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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1537651

Phase-dependent iron depletion differentially regulates the niche of intestinal stem cells in experimental colitis via ERK/STAT3 signaling pathway

Provisionally accepted
Shubin Wang Shubin Wang Xiangjun Liu Xiangjun Liu *Lu Xu Lu Xu *Jinyi Lang Jinyi Lang *Dengqun Liu Dengqun Liu *
  • Sichuan Cancer Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China

The final, formatted version of the article will be published soon.

    Background: Ulcerative colitis (UC) is a global gastrointestinal disease, which is mainly caused by both dysfunctional epithelial barrier and inflammation response. Iron is a critical fundamental element for both the maintenance of homeostasis and the mediation of inflammation in many tissues. However, the role and mechanism of iron in the phase of enteritis and the subsequent repairing phase of intestinal stem cells has not been elucidated. In this study, we aimed to explore whether and how iron depletion would affect the occurrence and outcome of experimental colitis.Iron depletion was realized by deferoxamine (DFO) at either the early stage or late stage of dextran sulfate sodium (DSS) induced experimental colitis in mice. The gross images of colons, general health, histology, barrier integrity, and qRT-PCR were performed. Meanwhile, cell culture and colonic organoids were used to examine the influence of iron depletion in vitro. Signaling pathway and inflammatory infiltration were investigated by immunostaining.Results: Iron depletion within the early stage of DSS treatment significantly inhibited the onset of the inflammatory response, maintained the integrity of the colonic epithelium, and preserved the activity of intestinal stem cells (ISCs) both in vivo and in vitro. However, both continuous iron depletion by DFO and late DFO treatment aggravated colonic injury and postponed the recovery from colitis. Early DFO-induced iron depletion was able to maintain the p-STAT3 and p-ERK1/2 signaling pathways within the colonic epithelium at the early phase of colitis, but late DFO treatment inhibited the activity of these two pathways.Our study demonstrated that the manipulation of iron depletion by DFO might greatly affect the outcomes of experimental colitis in a phase-dependent manner, which suggests that the balance of iron metabolism might be an effective therapeutic target for the clinical treatment of IBD patients.

    Keywords: Deferoxamine, Iron, intestinal stem cell, Organoid, Colitis

    Received: 03 Dec 2024; Accepted: 09 Jan 2025.

    Copyright: © 2025 Wang, Liu, Xu, Lang and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Xiangjun Liu, Sichuan Cancer Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
    Lu Xu, Sichuan Cancer Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
    Jinyi Lang, Sichuan Cancer Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
    Dengqun Liu, Sichuan Cancer Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.