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Although the pathological function of various hepatic cells in fibrogenesis is identified, the crosstalk between them remains obscure. The present study demonstrates that hepatic expression of adipocyte fatty acid binding protein (A\u2010FABP) is induced especially in the liver sinusoidal endothelial cells (LSECs) in mice after bile duct ligation (BDL). Genetic ablation and pharmacological inhibition of A\u2010FABP attenuate BDL\u2010 or carbon tetrachloride\u2010induced liver fibrosis in mice associating with reduced collagen accumulation, LSEC capillarization, and hepatic stellate cell (HSC) activation. Mechanistically, elevated A\u2010FABP promotes LSEC capillarization by activating Hedgehog signaling, thus impairs the gatekeeper function of LSEC on HSC activation. LSEC\u2010derived A\u2010FABP also acts on HSCs in paracrine manner to potentiate the transactivation of transforming growth factor\n                    <jats:italic>\u03b2<\/jats:italic>\n                    1 (TGF\n                    <jats:italic>\u03b2<\/jats:italic>\n                    1) by activating c\u2010Jun N\u2010terminal kinase\u00a0(JNK)\/c\u2010Jun signaling. Elevated TGF\n                    <jats:italic>\u03b2<\/jats:italic>\n                    1 subsequently exaggerates liver fibrosis. These findings uncover a novel pathological mechanism of liver fibrosis in which LSEC\u2010derived A\u2010FABP is a key regulator modulating the onset and progression of the disease. Targeting A\u2010FABP may represent a potential approach against liver fibrosis.\n                  <\/jats:p>","DOI":"10.1002\/advs.202003721","type":"journal-article","created":{"date-parts":[[2021,3,27]],"date-time":"2021-03-27T03:57:20Z","timestamp":1616817440000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":93,"title":["Adipocyte Fatty Acid Binding Protein Promotes the Onset and Progression of Liver Fibrosis via Mediating the Crosstalk between Liver Sinusoidal Endothelial Cells and Hepatic Stellate Cells"],"prefix":"10.1002","volume":"8","author":[{"given":"Xiaoping","family":"Wu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology LKS Faculty of Medicine the University of Hong Kong  Hong Kong 999077 China"},{"name":"Department of Pharmacology and Pharmacy LKS Faculty of Medicine the University of Hong Kong  Hong Kong 999077 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingling","family":"Shu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology LKS Faculty of Medicine the University of Hong Kong  Hong Kong 999077 China"},{"name":"Department of Medicine LKS Faculty of Medicine the University of Hong Kong  Hong Kong 999077 China"},{"name":"State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat\u2010sen University Cancer Center  Guangzhou 510060 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology LKS Faculty of Medicine the University of Hong Kong  Hong Kong 999077 China"},{"name":"Department of Pharmacology and Pharmacy LKS Faculty of Medicine the University of Hong Kong  Hong Kong 999077 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacy LKS Faculty of Medicine the University of Hong Kong  Hong Kong 999077 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiuyu","family":"Zong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology LKS Faculty of Medicine the University of Hong Kong  Hong Kong 999077 China"},{"name":"Department of Pharmacology and Pharmacy LKS Faculty of Medicine the University of Hong Kong  Hong Kong 999077 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lai Yee","family":"Cheong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology LKS Faculty of Medicine the University of Hong Kong  Hong Kong 999077 China"},{"name":"Department of Medicine LKS Faculty of Medicine the University of Hong Kong  Hong Kong 999077 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dewei","family":"Ye","sequence":"additional","affiliation":[{"name":"Joint Laboratory of Guangdong and Hong Kong on Metabolic Diseases Guangdong Pharmaceutical University  Guangzhou 510000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen S. 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