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Hepatic stellate cells (HSCs), by trans\u2010differentiating into myofibroblasts, are the principal mediator of liver fibrosis. In the present study we investigated the involvement of macrophage\u2010derived C\u2010C motif chemokine ligand 7 (CCL7) in this process. We report that mice harboring macrophage conditional knockout (CKO) of BRG1, a chromatin remodeling protein, displayed diminished liver fibrosis compared to wild type littermates. Co\u2010culture with macrophages from WT, but not CKO, mice enhanced HSC\u2010myofibroblast transition. RNA\u2010seq identified CCL7 as a target for BRG1. Depletion of CCL7 disrupted the crosstalk between macrophages and HSCs. On the contrary, recombinant CCL7 stimulated HSC\u2010myofibroblast transition. Importantly, CCL7 blockade with a neutralizing antibody attenuated liver fibrosis in mice. Transcriptomic analysis indicated that CCL7 activated sterol response element binding protein 2 (SREBP2) to modulate intracellular cholesterol levels during HSC\u2010myofibroblast transition. Consistently, cholesterol depletion with methyl\u2010beta\u2010cyclodextrin (M\u03b2CD) blocked HSC\u2010myofibroblast transition and mitigated liver fibrosis. Finally, a positive correlation between CCL7 levels in peripheral blood monocytic cells (PBMCs) and myofibroblast markers in liver tissues was identified in patients with cirrhosis. In conclusion, our data uncover an uncanonical role for CCL7 in liver fibrosis by directly promoting HSC\u2010myofibroblast transition.<\/jats:p>","DOI":"10.1096\/fj.202600972r","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T11:15:53Z","timestamp":1778584553000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["C\u2013C Motif Chemokine Ligand 7 Promotes\n                    <scp>HSC<\/scp>\n                    \u2010Myofibroblast Transition and Liver Fibrosis by Enabling\n                    <scp>SREBP2<\/scp>\n                    \u2010Dependent Cholesterologenesis"],"prefix":"10.1096","volume":"40","author":[{"given":"Weichun","family":"Xiao","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, School of Basic Medical Sciences Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Guo","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Research, College of Agriculture and Biology Liaocheng University  Liaocheng China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aoqi","family":"Kang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Targeted Intervention of Cardiovascular Disease and Collaborative Innovation Center for Cardiovascular Translational Medicine Nanjing Medical University  Nanjing China"},{"name":"State Key Laboratory of Natural Medicines, Department of Pharmacology China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinbo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, School of Basic Medical Sciences Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qihang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, School of Basic Medical Sciences Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangqiao","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, School of Basic Medical Sciences Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiulian","family":"Miao","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Research, College of Agriculture and Biology Liaocheng University  Liaocheng China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,12]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"661","article-title":"The Current Economic Burden of Cirrhosis","volume":"7","author":"Neff G. 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