Wang Shubin, Liu Xiangjun, Xu Lu, Lang Jinyi, Liu Dengqun
Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Cancer Hospital & Institute, Sichuan Provincial Engineering Research Center for Tumor Organoids and Clinical Transformation, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Department of Experimental Research, Sichuan Cancer Hospital & Institute, Sichuan Provincial Engineering Research Center for Tumor Organoids and Clinical Transformation, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Front Immunol. 2025 Jan 30;16:1537651. doi: 10.3389/fimmu.2025.1537651. eCollection 2025.
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 . Signaling pathway and inflammatory infiltration were investigated by immunostaining.
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 and . 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.
溃疡性结肠炎（UC）是一种全球性胃肠道疾病，主要由上皮屏障功能障碍和炎症反应引起。铁是许多组织维持内稳态和介导炎症的关键基本元素。然而，铁在肠炎阶段及随后肠道干细胞修复阶段的作用和机制尚未阐明。在本研究中，我们旨在探讨铁缺乏是否以及如何影响实验性结肠炎的发生和结局。
通过去铁胺（DFO）在葡聚糖硫酸钠（DSS）诱导的小鼠实验性结肠炎的早期或晚期实现铁缺乏。对结肠的大体图像、一般健康状况、组织学、屏障完整性和定量逆转录聚合酶链反应（qRT-PCR）进行检测。同时，使用细胞培养和结肠类器官来研究铁缺乏的影响。通过免疫染色研究信号通路和炎症浸润情况。
在DSS治疗早期进行铁缺乏显著抑制炎症反应的发生，维持结肠上皮的完整性，并在[此处原文似乎缺失部分内容]和[此处原文似乎缺失部分内容]时均保留肠道干细胞（ISC）的活性。然而，DFO持续铁缺乏和晚期DFO治疗均加重结肠损伤并延迟结肠炎的恢复。早期DFO诱导的铁缺乏能够在结肠炎早期维持结肠上皮内的p-STAT3和p-ERK1/2信号通路，但晚期DFO治疗抑制了这两条通路的活性。
我们的研究表明，通过DFO进行铁缺乏的调控可能以阶段依赖性方式极大地影响实验性结肠炎的结局，这表明铁代谢平衡可能是IBD患者临床治疗的有效治疗靶点。
Zotero 插件
