ECM1 is an essential factor for the determination of M1 macrophage polarization in IBD in response to LPS stimulation.
Yaguang ZhangXuezhen LiZhongguang LuoLiyan MaSongling ZhuZhishuo WangJing WenShipeng ChengWangpeng GuQiaoshi LianXinhao ZhaoWeiguo FanZhiyang LingJing YeSong Guo ZhengDangsheng LiHongyan WangJie LiuBing SunPublished in: Proceedings of the National Academy of Sciences of the United States of America (2020)
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.
Keyphrases
- extracellular matrix
- oxidative stress
- signaling pathway
- poor prognosis
- ulcerative colitis
- inflammatory response
- adipose tissue
- high glucose
- multiple sclerosis
- endothelial cells
- drug induced
- binding protein
- type diabetes
- gene expression
- rheumatoid arthritis
- cell proliferation
- high resolution
- nitric oxide
- transcription factor
- lps induced
- long non coding rna
- mass spectrometry
- peripheral blood
- wild type
- protein protein
- combination therapy
- pluripotent stem cells