Targeting SLC7 A11 Ameliorates Ulcerative Colitis by Promoting Efferocytosis Through the ERK1/2 Pathway.

IF 4.5 2区医学 Q2 CELL BIOLOGY

Inflammation Pub Date : 2025-05-13 DOI:10.1007/s10753-025-02312-6

Meiyi You, Jichang Li, Xin Wang, Yucun Liu, Shanwen Chen, Pengyuan Wang

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引用次数: 0

Abstract

Objective and design: This study investigates the effect and underlying mechanism of targeting SLC7A11 in mitigating dextran sulfate sodium (DSS)-induced intestinal inflammation and injury in colitis.

Methods: We utilized wild-type and SLC7A11^-/+ mice to assess the inflammatory damage in DSS-induced colitis in vivo. In vitro, colon tissues from patients with ulcerative colitis were analyzed to compare SLC7A11 expression between inflamed and non-inflamed regions. Further mechanistic insights were obtained using Caco-2 cells and bone marrow-derived dendritic cells (BMDCs).

Results: In human colon tissues, SLC7A11 expression was significantly elevated in inflamed regions compared to non-inflamed areas, particularly in dendritic cells. In vivo inhibition of SLC7A11 markedly alleviated DSS-induced colitis symptoms. In vitro, suppressing SLC7A11 restored the integrity of the Caco-2 monolayer intestinal epithelial model. Both knockout and inhibition of SLC7A11 enhanced ERK1/2 phosphorylation and increased efferocytosis in BMDCs.

Conclusions: Targeting SLC7A11 augments dendritic cell efferocytosis and preserves intestinal epithelial barrier function, potentially offering a therapeutic avenue for alleviating ulcerative colitis.

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靶向SLC7 A11通过ERK1/2通路促进Efferocytosis改善溃疡性结肠炎

目的与设计：本研究探讨靶向SLC7A11在减轻葡聚糖硫酸钠（DSS）诱导的结肠炎肠道炎症和损伤中的作用及其机制。方法：采用野生型和SLC7A11-/+小鼠进行dss诱导结肠炎的体内炎症损伤评估。在体外，对溃疡性结肠炎患者的结肠组织进行分析，比较SLC7A11在炎症区域和非炎症区域的表达。使用Caco-2细胞和骨髓来源的树突状细胞（bmdc）获得了进一步的机制见解。结果：在人类结肠组织中，SLC7A11在炎症区域的表达明显高于非炎症区域，特别是在树突状细胞中。体内抑制SLC7A11可显著缓解dss诱导的结肠炎症状。在体外，抑制SLC7A11可恢复Caco-2单层肠上皮模型的完整性。SLC7A11敲除和抑制均可增强BMDCs中ERK1/2的磷酸化和efferocytosis的增加。结论：靶向SLC7A11可增强树突状细胞胞吐并保持肠上皮屏障功能，可能为缓解溃疡性结肠炎提供治疗途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Inflammation 医学-免疫学

CiteScore

9.70

自引率

0.00%

发文量

168

审稿时长

3.0 months

期刊介绍： Inflammation publishes the latest international advances in experimental and clinical research on the physiology, biochemistry, cell biology, and pharmacology of inflammation. Contributions include full-length scientific reports, short definitive articles, and papers from meetings and symposia proceedings. The journal''s coverage includes acute and chronic inflammation; mediators of inflammation; mechanisms of tissue injury and cytotoxicity; pharmacology of inflammation; and clinical studies of inflammation and its modification.