PMID- 31980528 OWN - NLM STAT- MEDLINE DCOM- 20200511 LR - 20200724 IS - 1091-6490 (Electronic) IS - 0027-8424 (Print) IS - 0027-8424 (Linking) VI - 117 IP - 6 DP - 2020 Feb 11 TI - ECM1 is an essential factor for the determination of M1 macrophage polarization in IBD in response to LPS stimulation. PG - 3083-3092 LID - 10.1073/pnas.1912774117 [doi] AB - 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. FAU - Zhang, Yaguang AU - Zhang Y AUID- ORCID: 0000-0002-2417-6516 AD - 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; zhangyaguang@sibcb.ac.cn jieliu@fudan.edu.cn bsun@sibs.ac.cn. FAU - Li, Xuezhen AU - Li X AD - 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. FAU - Luo, Zhongguang AU - Luo Z AD - Department of Digestive Diseases, Huashan Hospital, Fudan University, 200040 Shanghai, China. FAU - Ma, Liyan AU - Ma L AD - 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. FAU - Zhu, Songling AU - Zhu S AD - 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. AD - School of Life Sciences, University of Science and Technology of China, 230022 Hefei, China. FAU - Wang, Zhishuo AU - Wang Z AD - 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. FAU - Wen, Jing AU - Wen J AD - 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. AD - School of Life Science and Technology, ShanghaiTech University, 201210 Shanghai, China. FAU - Cheng, Shipeng AU - Cheng S AD - 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. FAU - Gu, Wangpeng AU - Gu W AD - 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. AD - School of Life Sciences, University of Science and Technology of China, 230022 Hefei, China. FAU - Lian, Qiaoshi AU - Lian Q AD - 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. FAU - Zhao, Xinhao AU - Zhao X AD - Chinese Academy of Sciences Key Laboratory of Molecular Virology & Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, 200031 Shanghai, China. FAU - Fan, Weiguo AU - Fan W AUID- ORCID: 0000-0002-2382-5473 AD - Chinese Academy of Sciences Key Laboratory of Molecular Virology & Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, 200031 Shanghai, China. FAU - Ling, Zhiyang AU - Ling Z AD - 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. FAU - Ye, Jing AU - Ye J AD - 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. AD - School of Life Science and Technology, ShanghaiTech University, 201210 Shanghai, China. FAU - Zheng, Songguo AU - Zheng S AUID- ORCID: 0000-0002-5611-4774 AD - Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210. FAU - Li, Dangsheng AU - Li D AD - 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. FAU - Wang, Hongyan AU - Wang H AD - 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. FAU - Liu, Jie AU - Liu J AD - Department of Digestive Diseases, Huashan Hospital, Fudan University, 200040 Shanghai, China; zhangyaguang@sibcb.ac.cn jieliu@fudan.edu.cn bsun@sibs.ac.cn. AD - Institutes of Biomedical Sciences of Shanghai Medical School, Fudan University, 200032 Shanghai, China. FAU - Sun, Bing AU - Sun B AD - 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; zhangyaguang@sibcb.ac.cn jieliu@fudan.edu.cn bsun@sibs.ac.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200124 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (ECM1 protein, human) RN - 0 (Ecm1 protein, mouse) RN - 0 (Extracellular Matrix Proteins) RN - 0 (Lipopolysaccharides) RN - 0 (STAT5 Transcription Factor) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) RN - EC 3.5.3.1 (Arginase) SB - IM MH - Animals MH - Arginase/metabolism MH - Disease Models, Animal MH - Extracellular Matrix Proteins/genetics/*metabolism MH - Granulocyte-Macrophage Colony-Stimulating Factor/metabolism MH - Humans MH - Inflammatory Bowel Diseases/*metabolism/pathology MH - Intestines/pathology MH - Lipopolysaccharides/pharmacology MH - Macrophage Activation/drug effects/*physiology MH - Macrophages/drug effects/*metabolism MH - Mice MH - Mice, Knockout MH - STAT5 Transcription Factor/metabolism MH - Signal Transduction PMC - PMC7022174 OTO - NOTNLM OT - ARG1 OT - ECM1 OT - GM-CSF OT - IBD OT - STAT5 COIS- The authors declare no competing interest. EDAT- 2020/01/26 06:00 MHDA- 2020/05/12 06:00 PMCR- 2020/07/24 CRDT- 2020/01/26 06:00 PHST- 2020/01/26 06:00 [pubmed] PHST- 2020/05/12 06:00 [medline] PHST- 2020/01/26 06:00 [entrez] PHST- 2020/07/24 00:00 [pmc-release] AID - 1912774117 [pii] AID - 201912774 [pii] AID - 10.1073/pnas.1912774117 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2020 Feb 11;117(6):3083-3092. doi: 10.1073/pnas.1912774117. Epub 2020 Jan 24.