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The receptor tyrosine kinase (RTK) signal pathway plays an important role in the process of SSc, and Grb2\u2010associated binding protein (GAB) is crucial in activating RTK signalling. A previous study found elevated levels of GAB1 in bleomycin (BLM)\u2010induced fibrotic lungs, but the effects of GAB1 in SSc remain unclear. Our aim was to investigate whether GAB1 was dysregulated and its potential role in SSc. Compared with healthy donors, we found GAB1 expression was 1.6\u2010fold higher in peripheral blood mononuclear cells (PBMC), 2.5\u2010fold higher in CD4\u00a0+\u00a0T cells, and 2\u2010fold higher in skin from of SSc patients (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.01). At the same time, the levels of type one collagen (COLI) were also significantly increased (1.8\u2010fold higher) in SSc skin. Additionally, BLM\u2010induced SSc mice showed mRNA levels of <jats:italic>Gab1<\/jats:italic> 2\u2010fold higher than saline\u2010treated controls, and <jats:italic>Gab1<\/jats:italic> expression correlated positively with collagen content. A further in vitro study showed silencing of <jats:italic>GAB1<\/jats:italic> suppressed inflammatory gene expression in TNF\u2010\u03b1 induced fibroblasts. Additionally, <jats:italic>GAB1<\/jats:italic> deficiency prominently inhibited cell proliferation and reduced COLI protein levels in TGF\u2010\u03b2 induced fibroblasts. Taken together, these data suggest that GAB1 has a relatively high expression rate in SSc, and knockdown of <jats:italic>GAB1<\/jats:italic> may attenuate SSc by stimulating inflammatory and fibrotic processes.<\/jats:p>","DOI":"10.1111\/exd.14033","type":"journal-article","created":{"date-parts":[[2019,9,10]],"date-time":"2019-09-10T18:48:37Z","timestamp":1568141317000},"page":"1313-1320","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Increased expression of GAB1 promotes inflammation and fibrosis in systemic sclerosis"],"prefix":"10.1111","volume":"28","author":[{"given":"Xiangguang","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Dermatology Huashan Hospital Fudan University Shanghai China"},{"name":"State Key Laboratory of Genetic Engineering Collaborative Innovation Center for Genetics and Development School of Life Sciences Fudan University Shanghai 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Development School of Life Sciences Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Engineering Collaborative Innovation Center for Genetics and Development School of Life Sciences Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyun","family":"Ma","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Engineering Collaborative Innovation Center for Genetics and Development School of Life Sciences Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Xia","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Engineering Collaborative Innovation Center for Genetics and Development School of Life Sciences Fudan University Shanghai 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2765-0620","authenticated-orcid":false,"given":"Jiucun","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Engineering Collaborative Innovation Center for Genetics and Development School of Life Sciences Fudan University Shanghai China"},{"name":"Human Phenome Institute Fudan University Shanghai China"},{"name":"Institute of Rheumatology, Immunology and Allergy Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinhuan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Division of Rheumatology Shanghai TCM\u2010Integrated Hospital Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyu","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Dermatology Huashan Hospital Fudan University Shanghai China"},{"name":"Institute of Rheumatology, Immunology and Allergy Fudan University Shanghai China"},{"name":"Department of Dermatology Jing'an District Central Hospital Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,12,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/2397198318783926"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/2397198318764780"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.22451"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-012-2145-7"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39022"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2017.12.003"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.5301\/jsrd.5000238"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01865"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17060972"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1039\/C1MB05272A"},{"key":"e_1_2_8_12_1","first-page":"130","volume":"1","author":"Vaughan 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