Journal Article

ECM1 is an essential factor for the determination of M1 macrophage polarization in IBD in response to LPS stimulation

Ye, Jing, Lian, Qiaoshi, Wang, Zhishuo, Zhang, Yaguang, Wen, Jing, Li, Xuezhen, Luo, Zhongguang, Zhu, Songling, Liu, Jie, Ma, Liyan, Zhao, Xinhao, Wang, Hongyan, Ling, Zhiyang, Li, Dangsheng, Fan, Weiguo, Zheng, Songguo, Cheng, Shipeng, Gu, Wangpeng, Sun, Bing

2020

Overview

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 macrophagespecific 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.

• Publisher: National Academy of Sciences
• Subject: Animals / Arginase / Arginase - metabolism / Biological Sciences / Colony-stimulating factor / Dextran / Disease Models, Animal / Extracellular matrix / Extracellular Matrix Proteins - genetics / Extracellular Matrix Proteins - metabolism / Gastrointestinal system / Gastrointestinal tract / Granulocyte-macrophage colony stimulating factor / Granulocyte-Macrophage Colony-Stimulating Factor - metabolism / Humans / Immunology and Inflammation / Inflammatory bowel disease / Inflammatory bowel diseases / Inflammatory Bowel Diseases - metabolism / Inflammatory Bowel Diseases - pathology / Intestine / Intestines - pathology / Lipopolysaccharides / Lipopolysaccharides - pharmacology / Macrophage Activation - drug effects / Macrophage Activation - physiology / Macrophages / Macrophages - drug effects / Macrophages - metabolism / Matrix protein / Mice / Mice, Knockout / Pathogenesis / Phenotypes / Polarization / Signal Transduction / Sodium sulfate / Stat5 protein / STAT5 Transcription Factor - metabolism