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Article: 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

TitleAdipocyte 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
Authors
KeywordsA-FABP
TGFβ1
hepatic stellate cells
liver fibrosis
liver sinusoidal endothelial cells
Issue Date2021
PublisherWiley Open Access. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)2198-3844
Citation
Advanced Science, 2021, v. 8 n. 11, p. article no. 2003721 How to Cite?
AbstractDevelopment of liver fibrosis results in drastic changes in the liver microenvironment, which in turn accelerates disease progression. 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‐FABP) is induced especially in the liver sinusoidal endothelial cells (LSECs) in mice after bile duct ligation (BDL). Genetic ablation and pharmacological inhibition of A‐FABP attenuate BDL‐ or carbon tetrachloride‐induced liver fibrosis in mice associating with reduced collagen accumulation, LSEC capillarization, and hepatic stellate cell (HSC) activation. Mechanistically, elevated A‐FABP promotes LSEC capillarization by activating Hedgehog signaling, thus impairs the gatekeeper function of LSEC on HSC activation. LSEC‐derived A‐FABP also acts on HSCs in paracrine manner to potentiate the transactivation of transforming growth factor β1 (TGFβ1) by activating c‐Jun N‐terminal kinase (JNK)/c‐Jun signaling. Elevated TGFβ1 subsequently exaggerates liver fibrosis. These findings uncover a novel pathological mechanism of liver fibrosis in which LSEC‐derived A‐FABP is a key regulator modulating the onset and progression of the disease. Targeting A‐FABP may represent a potential approach against liver fibrosis.
Persistent Identifierhttp://hdl.handle.net/10722/299152
ISSN
2023 Impact Factor: 14.3
2023 SCImago Journal Rankings: 3.914
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWu, X-
dc.contributor.authorShu, L-
dc.contributor.authorZHANG, Z-
dc.contributor.authorLi, J-
dc.contributor.authorZONG, J-
dc.contributor.authorCheong, LY-
dc.contributor.authorYe, D-
dc.contributor.authorLam, KSL-
dc.contributor.authorSong, E-
dc.contributor.authorWang, C-
dc.contributor.authorXu, A-
dc.contributor.authorHoo, RLC-
dc.date.accessioned2021-04-28T02:26:52Z-
dc.date.available2021-04-28T02:26:52Z-
dc.date.issued2021-
dc.identifier.citationAdvanced Science, 2021, v. 8 n. 11, p. article no. 2003721-
dc.identifier.issn2198-3844-
dc.identifier.urihttp://hdl.handle.net/10722/299152-
dc.description.abstractDevelopment of liver fibrosis results in drastic changes in the liver microenvironment, which in turn accelerates disease progression. 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‐FABP) is induced especially in the liver sinusoidal endothelial cells (LSECs) in mice after bile duct ligation (BDL). Genetic ablation and pharmacological inhibition of A‐FABP attenuate BDL‐ or carbon tetrachloride‐induced liver fibrosis in mice associating with reduced collagen accumulation, LSEC capillarization, and hepatic stellate cell (HSC) activation. Mechanistically, elevated A‐FABP promotes LSEC capillarization by activating Hedgehog signaling, thus impairs the gatekeeper function of LSEC on HSC activation. LSEC‐derived A‐FABP also acts on HSCs in paracrine manner to potentiate the transactivation of transforming growth factor β1 (TGFβ1) by activating c‐Jun N‐terminal kinase (JNK)/c‐Jun signaling. Elevated TGFβ1 subsequently exaggerates liver fibrosis. These findings uncover a novel pathological mechanism of liver fibrosis in which LSEC‐derived A‐FABP is a key regulator modulating the onset and progression of the disease. Targeting A‐FABP may represent a potential approach against liver fibrosis.-
dc.languageeng-
dc.publisherWiley Open Access. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)2198-3844-
dc.relation.ispartofAdvanced Science-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectA-FABP-
dc.subjectTGFβ1-
dc.subjecthepatic stellate cells-
dc.subjectliver fibrosis-
dc.subjectliver sinusoidal endothelial cells-
dc.titleAdipocyte 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-
dc.typeArticle-
dc.identifier.emailWu, X: raxpwu@hku.hk-
dc.identifier.emailShu, L: shinyshu@hku.hk-
dc.identifier.emailLi, J: kimli07@hku.hk-
dc.identifier.emailCheong, LY: u3003285@connect.hku.hk-
dc.identifier.emailLam, KSL: ksllam@hku.hk-
dc.identifier.emailXu, A: amxu@hkucc.hku.hk-
dc.identifier.emailHoo, RLC: rubyhoo@hkucc.hku.hk-
dc.identifier.authorityLam, KSL=rp00343-
dc.identifier.authorityXu, A=rp00485-
dc.identifier.authorityHoo, RLC=rp01334-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1002/advs.202003721-
dc.identifier.pmid34105268-
dc.identifier.pmcidPMC8188197-
dc.identifier.scopuseid_2-s2.0-85103161915-
dc.identifier.hkuros322236-
dc.identifier.volume8-
dc.identifier.issue11-
dc.identifier.spagearticle no. 2003721-
dc.identifier.epagearticle no. 2003721-
dc.identifier.isiWOS:000633508600001-
dc.publisher.placeGermany-

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