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Article: Distinct mechanism of small-for-size fatty liver graft injury - Wnt4 signaling activates hepatic stellate cells

TitleDistinct mechanism of small-for-size fatty liver graft injury - Wnt4 signaling activates hepatic stellate cells
Authors
KeywordsAnimal models
Graft survival
Hepatic steatosis
Hepatic stellate cells
Liver transplantation
Marginal graft
Issue Date2010
PublisherBlackwell Munksgaard. The Journal's web site is located at http://www.blackwellpublishing.com/journals/AJT
Citation
American Journal Of Transplantation, 2010, v. 10 n. 5, p. 1178-1188 How to Cite?
AbstractIn this study, we aimed to investigate the significance of hepatic stellate cells (HSCs) activation in small-for-size fatty liver graft injury and to explore the underlying molecular mechanism in a rat liver transplantation model. A rat orthotopic liver transplantation model using fatty grafts (40% of fatty changes) and cirrhotic recipients was applied. Intragraft gene expression profiles, ultrastructure features and HSCs activation were compared among the rats received different types of grafts (whole vs. small-for-size, normal vs. fatty). The distinct molecular signature of small-for-size fatty graft injury was identified by cDNA microarray screening and confirmed by RT-PCR detection. In vitro functional studies were further conducted to investigate the direct effect of specific molecular signature on HSCs activation. HSCs activation was predominantly present in small-for-size fatty grafts during the first 2 weeks after transplantation, and was strongly correlated with progressive hepatic sinusoidal damage and significant upregulation of intragraft Wnt4 signaling pathway. In vitro suppression of Wnt4 expression could inhibit HSC activation directly. In conclusion, upregulation of Wnt4 signaling led to direct HSC activation and subsequently induced small-for-size fatty liver grafts injury. Discovery of this distinct mechanism may lay the foundation for prophylactic treatment for marginal graft injury in living donor liver transplantation. © 2010 The American Society of Transplantation and the American Society of Transplant Surgeons.
Persistent Identifierhttp://hdl.handle.net/10722/84085
ISSN
2015 Impact Factor: 5.669
2015 SCImago Journal Rankings: 2.792
ISI Accession Number ID
Funding AgencyGrant Number
University of Hong KongHKU5/CRF/08
Funding Information:

Funding sources: Seed funding for basic research, the University of Hong Kong and in part by the RGC Collaborative Research Fun (Ref no HKU5/CRF/08).

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorCheng, Qen_HK
dc.contributor.authorNg, KTen_HK
dc.contributor.authorFan, STen_HK
dc.contributor.authorLim, ZXen_HK
dc.contributor.authorGuo, DYen_HK
dc.contributor.authorLiu, XBen_HK
dc.contributor.authorLiu, Yen_HK
dc.contributor.authorPoon, RTPen_HK
dc.contributor.authorLo, CMen_HK
dc.contributor.authorMan, Ken_HK
dc.date.accessioned2010-09-06T08:48:45Z-
dc.date.available2010-09-06T08:48:45Z-
dc.date.issued2010en_HK
dc.identifier.citationAmerican Journal Of Transplantation, 2010, v. 10 n. 5, p. 1178-1188en_HK
dc.identifier.issn1600-6135en_HK
dc.identifier.urihttp://hdl.handle.net/10722/84085-
dc.description.abstractIn this study, we aimed to investigate the significance of hepatic stellate cells (HSCs) activation in small-for-size fatty liver graft injury and to explore the underlying molecular mechanism in a rat liver transplantation model. A rat orthotopic liver transplantation model using fatty grafts (40% of fatty changes) and cirrhotic recipients was applied. Intragraft gene expression profiles, ultrastructure features and HSCs activation were compared among the rats received different types of grafts (whole vs. small-for-size, normal vs. fatty). The distinct molecular signature of small-for-size fatty graft injury was identified by cDNA microarray screening and confirmed by RT-PCR detection. In vitro functional studies were further conducted to investigate the direct effect of specific molecular signature on HSCs activation. HSCs activation was predominantly present in small-for-size fatty grafts during the first 2 weeks after transplantation, and was strongly correlated with progressive hepatic sinusoidal damage and significant upregulation of intragraft Wnt4 signaling pathway. In vitro suppression of Wnt4 expression could inhibit HSC activation directly. In conclusion, upregulation of Wnt4 signaling led to direct HSC activation and subsequently induced small-for-size fatty liver grafts injury. Discovery of this distinct mechanism may lay the foundation for prophylactic treatment for marginal graft injury in living donor liver transplantation. © 2010 The American Society of Transplantation and the American Society of Transplant Surgeons.en_HK
dc.languageengen_HK
dc.publisherBlackwell Munksgaard. The Journal's web site is located at http://www.blackwellpublishing.com/journals/AJTen_HK
dc.relation.ispartofAmerican Journal of Transplantationen_HK
dc.subjectAnimal modelsen_HK
dc.subjectGraft survivalen_HK
dc.subjectHepatic steatosisen_HK
dc.subjectHepatic stellate cellsen_HK
dc.subjectLiver transplantationen_HK
dc.subjectMarginal graften_HK
dc.titleDistinct mechanism of small-for-size fatty liver graft injury - Wnt4 signaling activates hepatic stellate cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1600-6135&volume=10&issue=5&spage=1178&epage=1188&date=2010&atitle=Distinct+mechanism+of+small-for-size+fatty+liver+graft+injury--Wnt4+signaling+activates+hepatic+stellate+cellsen_HK
dc.identifier.emailNg, KT: ledodes@hku.hken_HK
dc.identifier.emailFan, ST: stfan@hku.hken_HK
dc.identifier.emailPoon, RTP: poontp@hku.hken_HK
dc.identifier.emailLo, CM: chungmlo@hkucc.hku.hken_HK
dc.identifier.emailMan, K: kwanman@hku.hken_HK
dc.identifier.authorityNg, KT=rp01720en_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.identifier.authorityPoon, RTP=rp00446en_HK
dc.identifier.authorityLo, CM=rp00412en_HK
dc.identifier.authorityMan, K=rp00417en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1111/j.1600-6143.2010.03102.xen_HK
dc.identifier.pmid20420630en_HK
dc.identifier.scopuseid_2-s2.0-77951249233en_HK
dc.identifier.hkuros170014en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77951249233&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume10en_HK
dc.identifier.issue5en_HK
dc.identifier.spage1178en_HK
dc.identifier.epage1188en_HK
dc.identifier.isiWOS:000276921600012-
dc.publisher.placeDenmarken_HK
dc.relation.projectLiver Transplantation Research Centre: A Multidisciplinary Study for Liver Graft Injury-
dc.identifier.scopusauthoridCheng, Q=16024087700en_HK
dc.identifier.scopusauthoridNg, KT=7403178513en_HK
dc.identifier.scopusauthoridFan, ST=7402678224en_HK
dc.identifier.scopusauthoridLim, ZX=25822628500en_HK
dc.identifier.scopusauthoridGuo, DY=36171425600en_HK
dc.identifier.scopusauthoridLiu, XB=36243863300en_HK
dc.identifier.scopusauthoridLiu, Y=25928027200en_HK
dc.identifier.scopusauthoridPoon, RTP=7103097223en_HK
dc.identifier.scopusauthoridLo, CM=7401771672en_HK
dc.identifier.scopusauthoridMan, K=7101754072en_HK

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