State Key Laboratory of Cell Biology, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 200031 Shanghai, China;
State Key Laboratory of Cell Biology, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 200031 Shanghai, China.
Proc Natl Acad Sci U S A. 2020 Feb 11;117(6):3083-3092. doi: 10.1073/pnas.1912774117. Epub 2020 Jan 24.
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 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.
炎症性肠病（IBD）是一种慢性复发性胃肠道疾病，其病理特征为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 的发病机制中具有重要作用。ECM1 在巨噬细胞中高度表达，特别是在炎症条件下组织浸润的巨噬细胞中，并且在 IBD 进展过程中 ECM1 的表达显著诱导。巨噬细胞特异性敲除 ECM1 导致精氨酸酶 1（ARG1）表达增加，并且在脂多糖（LPS）处理后向 M1 巨噬细胞表型的极化受损。机制研究表明，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 巨噬细胞极化。通过巨噬细胞中 基因的特异性敲除，可减轻葡聚糖硫酸钠诱导的 IBD 小鼠的病理变化。总之，我们的研究结果表明，ECM1 在促进 M1 巨噬细胞极化中具有重要功能，这对于控制肠道炎症和组织修复至关重要。
