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The fibrous lesions are produced by myofibroblasts, which differentiate from hepatic stellate cells (HSC). The myofibroblasts transcriptional networks remain poorly characterized. Previous studies have shown that the Forkhead box F1 (FOXF1) transcription factor is expressed in HSCs and stimulates their activation during acute liver injury; however, the role of FOXF1 in the progression of hepatic fibrosis is unknown. In the present study, we generated \u03b1SMACreER;Foxf1fl\/fl mice to conditionally inactivate Foxf1 in myofibroblasts during carbon tetrachloride-mediated liver fibrosis. Foxf1 deletion increased collagen depositions and disrupted liver architecture. Timp2 expression was significantly increased in Foxf1-deficient mice while MMP9 activity was reduced. RNA sequencing of purified liver myofibroblasts demonstrated that FOXF1 inhibits expression of pro-fibrotic genes, Col1\u03b12, Col5\u03b12, and Mmp2 in fibrotic livers and binds to active repressors located in promotors and introns of these genes. Overexpression of FOXF1 inhibits Col1a2, Col5a2, and MMP2 in primary murine HSCs in vitro. Altogether, FOXF1 prevents aberrant ECM depositions during hepatic fibrosis by repressing pro-fibrotic gene transcription in myofibroblasts and HSCs.<\/jats:p>","DOI":"10.1242\/bio.039800","type":"journal-article","created":{"date-parts":[[2019,1,22]],"date-time":"2019-01-22T19:01:02Z","timestamp":1548183662000},"source":"Crossref","is-referenced-by-count":15,"title":["The forkhead box F1 transcription factor inhibits collagen deposition and accumulation of myofibroblasts during liver fibrosis"],"prefix":"10.1242","author":[{"given":"Hannah M.","family":"Flood","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Cincinnati Children's Research Foundation, Cincinnati, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Bolte","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Cincinnati Children's Research Foundation, Cincinnati, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nupur","family":"Dasgupta","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Cincinnati Children's Research Foundation, Cincinnati, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akanksha","family":"Sharma","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Research Foundation, Cincinnati, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Cincinnati Children's Research Foundation, Cincinnati, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandrashekhar R.","family":"Gandhi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Cincinnati Children's Research Foundation, Cincinnati, Ohio, USA"},{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Research Foundation, Cincinnati, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya V.","family":"Kalin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Cincinnati Children's Research Foundation, Cincinnati, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3438-2660","authenticated-orcid":false,"given":"Vladimir V.","family":"Kalinichenko","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Cincinnati Children's Research Foundation, Cincinnati, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2019,1,1]]},"reference":[{"key":"2021042500021246700_BIO039800C1","doi-asserted-by":"publisher","first-page":"215","DOI":"10.2174\/1566523215666150126114634","article-title":"Foxf1 siRNA delivery to hepatic stellate cells by DBTC lipoplex formulations ameliorates fibrosis in livers of bile duct ligated mice","volume":"15","author":"Abshagen","year":"2015","journal-title":"Curr. 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