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Hepatic stellate cells (HSCs) are the major source of myofibroblasts in the liver. Follistatin like 1 (Fstl1) is a secreted glycoprotein induced by transforming growth factor-\u03b21 (TGF-\u03b21). However, the precise functions and regulation mechanisms of Fstl1 in liver fibrogenesis remains unclear.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Hepatic stellate cell (HSC) line LX-2 stimulated by TGF-\u03b21, primary culture of mouse HSCs and a model of liver fibrosis induced by CCl4 in mice was used to assess the effect of Fstl1 in vitro and in vivo.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Here, we found that Fstl1 was significantly up regulated in human and mouse fibrotic livers, as well as activated HSCs. Haplodeficiency of <jats:italic>Fstl1<\/jats:italic> or blockage of Fstl1 with a neutralizing antibody 22B6 attenuated CCl<jats:sub>4<\/jats:sub>-induced liver fibrosis in vivo. Fstl1 modulates TGF-\u03b21 classic Samd2 and non-classic JNK signaling pathways. Knockdown of Fstl1 in HSCs significantly ameliorated cell activation, cell migration, chemokines C-C Motif Chemokine Ligand 2 (CCL2) and C-X-C Motif Chemokine Ligand 8 (CXCL8) secretion and extracellular matrix (ECM) production, and also modulated microRNA-29a (miR29a) expression. Furthermore, we identified that Fstl1 was a target gene of miR29a. And TGF-\u03b21 induction of Fstl1 expression was partially through down regulation of <jats:italic>miR29a<\/jats:italic> in HSCs.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Our data suggests TGF-\u03b21-miR29a-Fstl1 regulatory circuit plays a key role in regulation the HSC activation and ECM production, and targeting Fstl1 may be a strategy for the treatment of liver fibrosis.<\/jats:p>\n\n<\/jats:sec><jats:sec>\n<jats:title>Graphical abstract<\/jats:title>\n\n<\/jats:sec>","DOI":"10.1186\/s12964-020-00610-0","type":"journal-article","created":{"date-parts":[[2020,9,15]],"date-time":"2020-09-15T12:02:55Z","timestamp":1600171375000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Targeting Follistatin like 1 ameliorates liver fibrosis induced by carbon tetrachloride through TGF-\u03b21-miR29a in mice"],"prefix":"10.1186","volume":"18","author":[{"given":"Xin-Yi","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilin","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Yu","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Song","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianhua","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng-Hong","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8861-7686","authenticated-orcid":false,"given":"Yan","family":"Geng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,9,15]]},"reference":[{"issue":"2","key":"610_CR1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1172\/JCI24282","volume":"115","author":"R Bataller","year":"2005","unstructured":"Bataller R, Brenner DA. 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