Farnesoid X Receptor Critically Determines the Fibrotic Response in Mice but Is Expressed to a Low Extent in Human Hepatic Stellate Cells and Periductal Myofibroblasts

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dc.contributor.authorFickert, Peter
dc.contributor.authorFuchsbichler, Andrea
dc.contributor.authorMoustafa, Tarek
dc.contributor.authorWagner, Martin
dc.contributor.authorZollner, Gernot
dc.contributor.authorHalilbasic, Emina
dc.contributor.authorStoeger, Ulrike
dc.contributor.authorArrese, Marco
dc.contributor.authorPizarro, Margarita
dc.contributor.authorSolis, Nancy
dc.contributor.authorCarrasco, Gonzalo
dc.contributor.authorCaligiuri, Alessandra
dc.contributor.authorSombetzki, Martina
dc.contributor.authorReisinger, Emil
dc.contributor.authorTsybrovskyy, Oleksiy
dc.contributor.authorZatloukal, Kurt
dc.contributor.authorDenk, Helmut
dc.contributor.authorJaeschke, Hartmut
dc.contributor.authorPinzani, Massimo
dc.contributor.authorTrauner, Michael
dc.date.accessioned2024-01-10T13:48:22Z
dc.date.available2024-01-10T13:48:22Z
dc.date.issued2009
dc.description.abstractThe nuclear bile acid receptor, farnesoid X receptor (FXR), may play a pivotal role in liver fibrosis. We tested the impact of genetic FXR ablation in four different mouse models. Hepatic fibrosis was induced in wild-type and FXR knock-out mice (FXR-/-) by CCl4 intoxication, 3,5-diethoxycarbonyl-1,4-dihydrocollidine feeding, common bile duct ligation, or Schistosoma mansoni (S.m.)-infection. In addition, we determined nuclear receptor expression levels (FXR, pregnane X receptor (PXR), vitamin D receptor, constitutive androstane receptor (CAR), small heterodimer partner (SHP)) in mouse hepatic stellate cells (HSCs), portal myofibroblasts (MFBs), and human HSCs. Cell type-specific FXR protein expression was determined by immunohistochemistry in five mouse models and prototypic human fibrotic liver diseases. Expression of nuclear receptors was much lower in mouse and human HSCs/MFBs compared with total liver expression with the exception of vitamin D receptor. FXR protein was undetectable in mouse and human HSCs and MFBs. FXR loss had no effect in CCl4-intoxicated and S. m.-infected mice, but significantly decreased liver fibrosis of the bitiary type (common bile duct ligation, 3,5-diethoxycarbonyl-1,4-dihydrocoUidine). These data suggest that FXR loss significantly reduces fibrosis of the biliary type, but has no impact on non-cholestatic liver fibrosis. Since there is no FXR expression in HSCs and MFBs in liver fibrosis, our data indicate that these cells may not represent direct therapeutic targets for FXR ligands. (Am J Pathol 2009, 175;2392-2405; DOI: 10.2353/ajpath.2009.090114)
dc.description.funderAustrian Science Fund FWF
dc.fechaingreso.objetodigital2024-05-22
dc.format.extent14 páginas
dc.fuente.origenWOS
dc.identifier.doi10.2353/ajpath.2009.090114
dc.identifier.eissn1525-2191
dc.identifier.issn0002-9440
dc.identifier.pubmedidMEDLINE:19910507
dc.identifier.urihttps://doi.org/10.2353/ajpath.2009.090114
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/79358
dc.identifier.wosidWOS:000272600600016
dc.information.autorucMedicina;Arrese M;S/I;76095
dc.information.autorucMedicina;Carrasco G;S/I;14818
dc.information.autorucMedicina;Pizarro M;S/I;102250
dc.information.autorucMedicina;Solís N;S/I;102379
dc.issue.numero6
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final2405
dc.pagina.inicio2392
dc.publisherELSEVIER SCIENCE INC
dc.revistaAMERICAN JOURNAL OF PATHOLOGY
dc.rightsacceso restringido
dc.subjectFAMILIAL INTRAHEPATIC CHOLESTASIS
dc.subjectBILE-ACID RECEPTOR
dc.subjectNUCLEAR RECEPTOR
dc.subjectABC TRANSPORTER
dc.subjectOBSTRUCTIVE CHOLESTASIS
dc.subjectCHENODEOXYCHOLIC ACID
dc.subjectADAPTIVE RESPONSE
dc.subjectEXPORT PUMP
dc.subjectMOUSE MODEL
dc.subjectFXR
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleFarnesoid X Receptor Critically Determines the Fibrotic Response in Mice but Is Expressed to a Low Extent in Human Hepatic Stellate Cells and Periductal Myofibroblasts
dc.typeartículo
dc.volumen175
sipa.codpersvinculados76095
sipa.codpersvinculados14818
sipa.codpersvinculados102250
sipa.codpersvinculados102379
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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