Inflammatory bowel disease (IBD) comprises chronic relapsing disorders of the gastrointestinal tract characterized pathologically by intestinal inflammation and epithelial injury. Here, we uncover a function of extracellular matrix protein 1 (ECM1) in promoting the pathogenesis of human and mouse IBD. ECM1 was highly expressed in macrophages, particularly tissue-infiltrated macrophages under inflammatory conditions, and ECM1 expression was significantly induced during IBD progression. The macrophage-specific knockout of ECM1 resulted in increased arginase 1 (ARG1) expression and impaired polarization into the M1 macrophage phenotype after lipopolysaccharide (LPS) treatment. A mechanistic study showed that ECM1 can regulate M1 macrophage polarization through the granulocyte-macrophage colony-stimulating factor/STAT5 signaling pathway. Pathological changes in mice with dextran sodium sulfate-induced IBD were alleviated by the specific knockout of the ECM1 gene in macrophages. Taken together, our findings show that ECM1 has an important function in promoting M1 macrophage polarization, which is critical for controlling inflammation and tissue repair in the intestine.

中文翻译：

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ECM1是确定IBD响应LPS刺激的M1巨噬细胞极化的必要因素。

炎症性肠病（IBD）包括胃肠道的慢性复发性疾病，其病理特征是肠道炎症和上皮损伤。在这里，我们发现细胞外基质蛋白1（ECM1）在促进人类和小鼠IBD发病机理中的功能。ECM1在炎症条件下的巨噬细胞，特别是组织浸润的巨噬细胞中高表达，并且在IBD进程中明显诱导ECM1表达。脂多糖（LPS）处理后，ECM1的巨噬细胞特异性敲除导致精氨酸酶1（ARG1）表达增加，并削弱了极化成M1巨噬细胞表型。机理研究表明，ECM1可以通过粒细胞-巨噬细胞集落刺激因子/ STAT5信号通路调节M1巨噬细胞的极化。巨噬细胞中ECM1基因的特异性敲除减轻了葡聚糖硫酸钠诱导的IBD小鼠的病理变化。综上所述，我们的发现表明ECM1在促进M1巨噬细胞极化方面具有重要功能，这对于控制肠道炎症和组织修复至关重要。