File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Conference Paper: The Role of Adipocyte Fatty Acid Binding Protein in the Development of Liver Fibrosis

TitleThe Role of Adipocyte Fatty Acid Binding Protein in the Development of Liver Fibrosis
Authors
Issue Date2018
PublisherAmerican Diabetes Association. The Journal's web site is located at http://diabetes.diabetesjournals.org/
Citation
American Diabetes Association 78th Scientific Sessions, Orlando, Florida, USA, 22-26 June 2018. In Diabetes, 2018, v. 67 n. Suppl. 1, p. A495, abstract no. 1866‑P How to Cite?
AbstractLiver fibrosis is the result of chronic liver injury and the first step toward the development of liver cirrhosis and hepatic carcinoma. Under the stress of damage factors, quiescent hepatic stellate cells (qHSCs) trans-differentiate into myofibroblast-like cells, and take the main role of extracellular matrix secretion contributing to the development of liver fibrosis. In recent clinical study, circulating level of A-FABP, was found to positively correlate with the stages of liver fibrosis and liver cirrhosis. Here, we investigate the role of A-FABP in the development of liver fibrosis. A-FABP knockout (A-FABP KO) mice and their wild type (WT) littermates were subjected to bile duct ligation (BDL) for two weeks to induce liver fibrosis. Plasma and hepatic A-FABP were significantly elevated in BDL treated WT mice. Liver sinusoidal endothelial cell (LSEC) was identified as the major cellular source of hepatic A-FABP in response to BDL. In the BDL treated groups, comparing to the WT mice, A-FABP KO mice showed significantly reduced collagen formation and HSC activation which were accompanied by an attenuated induction of hepatic expression of transforming growth factor beta 1 (TGFβ1), a central regulator in hepatic fibrogenesis. As the LSECs and HSCs are closely attached to each other, we hypothesize that LSECs-derived A-FABP may act in a paracrine manner to stimulate the expression of TGFβ1 in HSCs. Our in vitro study demonstrated that treatment of recombinant A-FABP protein (rA-FABP) significantly induced the expression of TGFβ1 in primary HSCs. Mechanistically, BDL induces the release of A-FABP from LSECs which stimulates the TGFβ1 gene transcription through enhancing the activator protein-1 (AP-1) activity on its promoter via upregulating the phosphorylation of c-Jun, a component of AP-1. In conclusion, A-FABP contributes to the development of liver fibrosis viaenhancing the expression of TGFβ1 in HSCs.
DescriptionPoster presentation - Integrated Physiology: Liver - no. 1866‑P
Persistent Identifierhttp://hdl.handle.net/10722/261980
ISSN
2019 Impact Factor: 7.72
2015 SCImago Journal Rankings: 5.185

 

DC FieldValueLanguage
dc.contributor.authorWu, X-
dc.contributor.authorShu, L-
dc.contributor.authorLam, KSL-
dc.contributor.authorXu, A-
dc.contributor.authorHoo, RLC-
dc.date.accessioned2018-09-28T04:51:18Z-
dc.date.available2018-09-28T04:51:18Z-
dc.date.issued2018-
dc.identifier.citationAmerican Diabetes Association 78th Scientific Sessions, Orlando, Florida, USA, 22-26 June 2018. In Diabetes, 2018, v. 67 n. Suppl. 1, p. A495, abstract no. 1866‑P-
dc.identifier.issn0012-1797-
dc.identifier.urihttp://hdl.handle.net/10722/261980-
dc.descriptionPoster presentation - Integrated Physiology: Liver - no. 1866‑P-
dc.description.abstractLiver fibrosis is the result of chronic liver injury and the first step toward the development of liver cirrhosis and hepatic carcinoma. Under the stress of damage factors, quiescent hepatic stellate cells (qHSCs) trans-differentiate into myofibroblast-like cells, and take the main role of extracellular matrix secretion contributing to the development of liver fibrosis. In recent clinical study, circulating level of A-FABP, was found to positively correlate with the stages of liver fibrosis and liver cirrhosis. Here, we investigate the role of A-FABP in the development of liver fibrosis. A-FABP knockout (A-FABP KO) mice and their wild type (WT) littermates were subjected to bile duct ligation (BDL) for two weeks to induce liver fibrosis. Plasma and hepatic A-FABP were significantly elevated in BDL treated WT mice. Liver sinusoidal endothelial cell (LSEC) was identified as the major cellular source of hepatic A-FABP in response to BDL. In the BDL treated groups, comparing to the WT mice, A-FABP KO mice showed significantly reduced collagen formation and HSC activation which were accompanied by an attenuated induction of hepatic expression of transforming growth factor beta 1 (TGFβ1), a central regulator in hepatic fibrogenesis. As the LSECs and HSCs are closely attached to each other, we hypothesize that LSECs-derived A-FABP may act in a paracrine manner to stimulate the expression of TGFβ1 in HSCs. Our in vitro study demonstrated that treatment of recombinant A-FABP protein (rA-FABP) significantly induced the expression of TGFβ1 in primary HSCs. Mechanistically, BDL induces the release of A-FABP from LSECs which stimulates the TGFβ1 gene transcription through enhancing the activator protein-1 (AP-1) activity on its promoter via upregulating the phosphorylation of c-Jun, a component of AP-1. In conclusion, A-FABP contributes to the development of liver fibrosis viaenhancing the expression of TGFβ1 in HSCs.-
dc.languageeng-
dc.publisherAmerican Diabetes Association. The Journal's web site is located at http://diabetes.diabetesjournals.org/-
dc.relation.ispartofDiabetes-
dc.relation.ispartofAmerican Diabetes Association 78th Scientific Sessions-
dc.titleThe Role of Adipocyte Fatty Acid Binding Protein in the Development of Liver Fibrosis-
dc.typeConference_Paper-
dc.identifier.emailShu, L: shinyshu@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.identifier.doi10.2337/db18-1866-P-
dc.identifier.hkuros292752-
dc.identifier.volume67-
dc.identifier.issueSuppl. 1-
dc.identifier.spageA495-
dc.identifier.epageA495-
dc.publisher.placeUnited States-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats