2025
Mechanistic insights into deoxynivalenol-Induced hepatic cholestasis via IRE1α/HNF1α/FXR signaling dysregulation in mice
Wu Y, Lin R, Yuan Q, Sun Y, Yuan Y, Jiang T, Jiang J, Mu P, Wen J, Deng Y. Mechanistic insights into deoxynivalenol-Induced hepatic cholestasis via IRE1α/HNF1α/FXR signaling dysregulation in mice. Ecotoxicology And Environmental Safety 2025, 301: 118489. PMID: 40513317, DOI: 10.1016/j.ecoenv.2025.118489.Peer-Reviewed Original ResearchFarnesoid X receptorTotal bile acidsBile acidsFXR functionPro-inflammatory cytokine expressionPro-inflammatory cascadeDON-induced toxicityTarget of farnesoid X receptorEndoplasmic reticulum stressMurine modelUnfolded protein responseHepatocellular injuryNuclear receptor signalingCytokine expressionHepatic cholestasisHepatocellular damageReceptor signalingSignaling dysregulationLiver pathologyCholestasisPharmacological targetsCentral mechanismsTherapeutic targetSignaling AxisUpregulate pro-inflammatory cytokine expressionChanges in the FXR-cistrome and alterations in bile acid physiology in Wilson disease
Wooton-Kee C, Yalamanchili H, Mohamed I, Hassan M, Setchell K, Rivas M, Coskun A, Putluri V, Putluri N, Jalal P, Schilsky M, Moore D. Changes in the FXR-cistrome and alterations in bile acid physiology in Wilson disease. Hepatology Communications 2025, 9: e0707. PMID: 40408300, PMCID: PMC12106221, DOI: 10.1097/hc9.0000000000000707.Peer-Reviewed Original ResearchConceptsWild-type miceFarnesoid X receptorWilson's diseaseNon-parenchymal cellsDistal intergenic regionsLiver bile acid concentrationWD patientsHealthy controlsMetabolic target genesFarnesoid X Receptor RegulationBile salt export pumpIntergenic regionFXR activationAutosomal recessive disorderBile acid homeostasisBile acid physiologyFarnesoid X receptor activationPromoter regionHomeostasis pathwaysBile acid metabolismDecreasing FXR activityTarget genesBile acid profilesMarker genesStress pathways
2024
Fecal deoxycholic acid associates with diet, intestinal microbes, and total bilirubin in primary sclerosing cholangitis
Chan C, Lemos M, Finnegan P, Gagnon W, Dean R, Yazdanafar M, Zepeda J, Vohl M, Trauner M, Korzenik J, Barbier O, Marco M, Bowlus C. Fecal deoxycholic acid associates with diet, intestinal microbes, and total bilirubin in primary sclerosing cholangitis. JHEP Reports 2024, 6: 101188. PMID: 39624235, PMCID: PMC11609371, DOI: 10.1016/j.jhepr.2024.101188.Peer-Reviewed Original ResearchPrimary sclerosing cholangitisMarkers of BA synthesisFecal deoxycholic acidInflammatory bowel diseaseCholestatic liver diseaseFarnesoid X receptorFarnesoid X receptor activationSclerosing cholangitisDisease progressionFecal bile acidsTotal bilirubinDuct primary sclerosing cholangitisBile acidsLiver diseaseMarker of clinical outcomeBA synthesisChronic cholestatic liver diseaseRRNA gene sequencesUrsodeoxycholic acid useDeoxycholic acidAbundance of BlautiaMarkers of disease progressionVariable disease progressionAssociated with total bilirubinSerum total bilirubin
2016
Sirtuin 1 activation alleviates cholestatic liver injury in a cholic acid–fed mouse model of cholestasis
Kulkarni SR, Soroka CJ, Hagey LR, Boyer JL. Sirtuin 1 activation alleviates cholestatic liver injury in a cholic acid–fed mouse model of cholestasis. Hepatology 2016, 64: 2151-2164. PMID: 27639250, PMCID: PMC5115990, DOI: 10.1002/hep.28826.Peer-Reviewed Original ResearchConceptsCholestatic liver injuryLiver injurySRT1720 administrationSIRT1 expressionCa dietMouse modelFibroblast growth factor 15Proliferator-activated receptor gamma coactivator 1Multidrug resistance-associated protein 2Peroxisome proliferator-activated receptor gamma coactivator 1Hepatic BA compositionHepatic BA synthesisGrowth factor 15Receptor gamma coactivator 1Resistance-associated protein 2Plasma alanine aminotransferasePlasma BA concentrationsCultured primary human hepatocytesNovel therapeutic targetSirtuin 1 activationFarnesoid X receptorMiR-34a expressionSIRT1 messenger RNACytochrome P450 7A1Bile acid sensor
2013
FXR silencing in human colon cancer by DNA methylation and KRAS signaling
Bailey AM, Zhan L, Maru D, Shureiqi I, Pickering CR, Kiriakova G, Izzo J, He N, Wei C, Baladandayuthapani V, Liang H, Kopetz S, Powis G, Guo GL. FXR silencing in human colon cancer by DNA methylation and KRAS signaling. AJP Gastrointestinal And Liver Physiology 2013, 306: g48-g58. PMID: 24177031, PMCID: PMC3920083, DOI: 10.1152/ajpgi.00234.2013.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaBile Acids and SaltsCarcinogenesisCell Line, TumorColonColonic NeoplasmsColonic PolypsDNA MethylationEpithelial-Mesenchymal TransitionGene SilencingHumansNeoplasm StagingProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)ras ProteinsReceptors, Cytoplasmic and NuclearSignal TransductionConceptsDNA methylationHuman colon cancerHuman colon cancer progressionMethyl-DNA immunoprecipitationRegulation of FXRFarnesoid X receptorMesenchymal transitionOncogenic signaling cascadesMouse knockout studiesReverse phase protein arrayColon cancer progressionDNA methyltransferase inhibitionFunction of FXRCancer Genome Atlas (TCGA) samplesColon cancer cell linesColon cancer samplesCancer Genome AtlasBisulfite sequencingMethylation patternsKnockout studiesColon cancer developmentSignaling cascadesMethyltransferase inhibitionTumor suppressorPhosphatidylinositol 4
2011
Dual farnesoid X receptor/TGR5 agonist INT‐767 reduces liver injury in the Mdr2−/− (Abcb4−/−) mouse cholangiopathy model by promoting biliary HCO output
Baghdasaryan A, Claudel T, Gumhold J, Silbert D, Adorini L, Roda A, Vecchiotti S, Gonzalez FJ, Schoonjans K, Strazzabosco M, Fickert P, Trauner M. Dual farnesoid X receptor/TGR5 agonist INT‐767 reduces liver injury in the Mdr2−/− (Abcb4−/−) mouse cholangiopathy model by promoting biliary HCO output. Hepatology 2011, 54: 1303-1312. PMID: 22006858, PMCID: PMC3744065, DOI: 10.1002/hep.24537.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphatasesAnalysis of VarianceAnimalsAnion Transport ProteinsATP Binding Cassette Transporter, Subfamily BBile Acids and SaltsBiliary Tract DiseasesCholic AcidsDisease Models, AnimalLiver DiseasesMaleMiceMice, Inbred C57BLRandom AllocationReceptors, Cytoplasmic and NuclearReceptors, G-Protein-CoupledStatistics, NonparametricConceptsFarnesoid X receptorINT-767Liver injuryChronic cholangiopathiesTGR5 agonistsINT-747Hepatic inflammationINT-777Bile secretionBiliary bile acid outputActivation of FXRNuclear farnesoid X receptorSerum liver enzymesBile acid outputBile acid homeostasisFXR-dependent mannerBile acid synthesisMembrane G protein-coupled receptorsG protein-coupled receptorsLiver transplantationProtein-coupled receptorsBiliary fibrosisAcid outputChow dietTherapeutic optionsNew insights on the pathogenesis of biliary cirrhosis provided by studies in FXR knockout mice
Fausther M, Dranoff JA. New insights on the pathogenesis of biliary cirrhosis provided by studies in FXR knockout mice. Journal Of Hepatology 2011, 55: 939-940. PMID: 21672564, PMCID: PMC3756144, DOI: 10.1016/j.jhep.2011.04.013.Peer-Reviewed Original ResearchHepatic stellate cellsHuman hepatic stellate cellsFarnesoid X receptorLiver fibrosisBiliary typeMouse modelCommon bile duct ligationNuclear bile acid receptorFXR protein expressionMouse hepatic stellate cellsFibrotic liver diseaseBile acid receptorBile duct ligationDifferent mouse modelsFXR knockout miceVitamin D receptorReceptor expression levelsDirect therapeutic targetsBiliary cirrhosisLiver diseaseHepatic fibrosisDuct ligationFXR expressionD receptorLiver expression
2008
ATP8B1 Deficiency Disrupts the Bile Canalicular Membrane Bilayer Structure in Hepatocytes, But FXR Expression and Activity Are Maintained
Cai S, Gautam S, Nguyen T, Soroka CJ, Rahner C, Boyer JL. ATP8B1 Deficiency Disrupts the Bile Canalicular Membrane Bilayer Structure in Hepatocytes, But FXR Expression and Activity Are Maintained. Gastroenterology 2008, 136: 1060-1069.e4. PMID: 19027009, PMCID: PMC3439851, DOI: 10.1053/j.gastro.2008.10.025.Peer-Reviewed Original ResearchMeSH Keywords4-Chloro-7-nitrobenzofurazanAdenosine TriphosphatasesAnimalsATP Binding Cassette Transporter, Subfamily B, Member 11ATP-Binding Cassette TransportersBile CanaliculiCaco-2 CellsChenodeoxycholic AcidDNA-Binding ProteinsGastrointestinal AgentsGene ExpressionHepatocytesHumansMultidrug Resistance-Associated Protein 2PhosphatidylserinesPhospholipid Transfer ProteinsRatsReceptors, Cytoplasmic and NuclearRNA, Small InterferingTranscription FactorsTransfectionConceptsAminophospholipid flippaseMessenger RNAMembrane bilayer structureCanalicular membraneFarnesoid X receptorRat hepatocytesSmall heterodimer partnerMembrane transportersNBD-phosphatidylserineHeterodimer partnerDeficiency disruptsLuminal accumulationMembrane disruptionRNAConflicting hypothesesRat cellsFlippaseProtein levelsProtein expressionX receptorExpressionBSEP functionATP8B1CellsMembrane
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