2023
Organic Anion Transporting Polypeptide (OATP) 1B3 is a Significant Transporter for Hepatic Uptake of Conjugated Bile Acids in Humans
Pan Q, Zhu G, Xu Z, Zhu J, Ouyang J, Tong Y, Zhao N, Zhang X, Cheng Y, Zhang L, Tan Y, Li J, Zhang C, Chen W, Cai S, Boyer J, Chai J. Organic Anion Transporting Polypeptide (OATP) 1B3 is a Significant Transporter for Hepatic Uptake of Conjugated Bile Acids in Humans. Cellular And Molecular Gastroenterology And Hepatology 2023, 16: 223-242. PMID: 37146714, PMCID: PMC10394288, DOI: 10.1016/j.jcmgh.2023.04.007.Peer-Reviewed Original ResearchConceptsBA uptake transportersBile duct ligationHepatic neutrophil infiltrationCholestatic liver injuryProinflammatory cytokine productionCholic acid dietAdaptive protective responseLiver-specific overexpressionWild-type miceConjugated bile acidsUptake transportersPrimary hepatocytesUDCA feedingNeutrophil infiltrationBDL miceLiver injuryCytokine productionBile flowDuct ligationOrganic anion transporting polypeptide (OATP) 1B3Conjugated BAsTransgenic miceHepatic uptakeBile acidsProtective responseRunt-related transcription factor-1 ameliorates bile acid–induced hepatic inflammation in cholestasis through JAK/STAT3 signaling
Zhang L, Pan Q, Zhang L, Xia H, Liao J, Zhang X, Zhao N, Xie Q, Liao M, Tan Y, Li Q, Zhu J, Li L, Fan S, Li J, Zhang C, Cai S, Boyer J, Chai J. Runt-related transcription factor-1 ameliorates bile acid–induced hepatic inflammation in cholestasis through JAK/STAT3 signaling. Hepatology 2023, 77: 1866-1881. PMID: 36647589, PMCID: PMC10921919, DOI: 10.1097/hep.0000000000000041.Peer-Reviewed Original ResearchConceptsJAK/STAT3Bile duct ligationInflammatory responseLiver injuryCholestatic patientsTranscription factor 1Duct ligationBile acidsLiver inflammatory responseCholestatic liver injuryHepatic inflammatory responseElevated bile acidsCholic acid dietFactor 1Cholic acid feedingLiver-specific ablationNew therapeutic targetsLiver-specific deletionCholestatic miceHepatic inflammationLiver inflammationInflammatory chemokinesHepatic expressionMouse modelAcid diet
2021
Adjunct Fenofibrate Up‐regulates Bile Acid Glucuronidation and Improves Treatment Response For Patients With Cholestasis
Gallucci GM, Trottier J, Hemme C, Assis DN, Boyer JL, Barbier O, Ghonem NS. Adjunct Fenofibrate Up‐regulates Bile Acid Glucuronidation and Improves Treatment Response For Patients With Cholestasis. Hepatology Communications 2021, 5: 2035-2051. PMID: 34558841, PMCID: PMC8631103, DOI: 10.1002/hep4.1787.Peer-Reviewed Original ResearchConceptsSerum bile acidsSerum alkaline phosphataseBile acidsTreatment responseIncomplete responseTotal serum bile acidsElevated serum alkaline phosphatasePeroxisome proliferator-activated receptor alphaProliferator-activated receptor alphaAlkaline phosphatasePrimary sclerosing cholangitisPrimary biliary cholangitisStandard of careSerum ALP levelsBile acid glucuronidationCytotoxic bile acidsPrimary human hepatocytesBA detoxificationFenofibrate therapySclerosing cholangitisAdult patientsBiliary cholangitisLiver failureCombination therapyImproved outcomesThe role of bile acids in cholestatic liver injury
Cai SY, Boyer JL. The role of bile acids in cholestatic liver injury. Annals Of Translational Medicine 2021, 9: 737-737. PMID: 33987435, PMCID: PMC8106037, DOI: 10.21037/atm-20-5110.Peer-Reviewed Original ResearchCholestatic liver injuryBile duct proliferationLiver injuryParenchymal cell deathBile acidsDuct proliferationImmune cellsStellate cellsProliferation of cholangiocytesSphingosine-1-phosphate receptor 2Bile acid receptorCell deathMajor cellular componentLiver inflammationClinical evidenceInflammatory cytokinesLiver fibrosisPathogenic rolePathologic effectsReceptor 2Mitochondrial injuryAcid receptorsClinical disordersInjuryOxidative stress
2020
Fenofibrate Improves Liver Function and Reduces the Toxicity of the Bile Acid Pool in Patients With Primary Biliary Cholangitis and Primary Sclerosing Cholangitis Who Are Partial Responders to Ursodiol
Ghonem NS, Auclair AM, Hemme CL, Gallucci GM, de la Rosa Rodriguez R, Boyer JL, Assis DN. Fenofibrate Improves Liver Function and Reduces the Toxicity of the Bile Acid Pool in Patients With Primary Biliary Cholangitis and Primary Sclerosing Cholangitis Who Are Partial Responders to Ursodiol. Clinical Pharmacology & Therapeutics 2020, 108: 1213-1223. PMID: 32480421, PMCID: PMC7886378, DOI: 10.1002/cpt.1930.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBile Acids and SaltsBiomarkersCholangitis, SclerosingCytokinesDrug Therapy, CombinationFemaleFenofibrateHumansInflammation MediatorsLiverLiver Cirrhosis, BiliaryLiver Function TestsMaleMiddle AgedPPAR alphaPrincipal Component AnalysisRetrospective StudiesTreatment OutcomeUrsodeoxycholic AcidYoung AdultConceptsPrimary sclerosing cholangitisPrimary biliary cholangitisBile acid metabolismSclerosing cholangitisBiliary cholangitisBile acidsAcid metabolismPeroxisome proliferator-activated receptor alphaProliferator-activated receptor alphaRetrospective observational studyBeneficial clinical effectsCholestatic liver diseasePro-inflammatory cytokinesBile acid metabolitesHealthy control subjectsBile acid poolSerum alkaline phosphataseAminotransferase abnormalitiesUrsodiol therapyFenofibrate therapyPartial respondersBile acid precursorsClinical effectsFenofibrate treatmentLiver diseaseThe Role of Bile Acid‐Mediated Inflammation in Cholestatic Liver Injury
Cai S, Li M, Boyer J. The Role of Bile Acid‐Mediated Inflammation in Cholestatic Liver Injury. 2020, 728-736. DOI: 10.1002/9781119436812.ch56.Peer-Reviewed Original ResearchCholestatic liver injuryBile acidsLiver injuryProinflammatory mediatorsInflammatory responseCauses of cholestasisAlcoholic liver diseasePrimary biliary cholangitisConjugated bile acidsEffects of drugsHepatic infiltrationBile acid transporterLiver transplantationViral hepatitisBiliary cholangitisBiliary cirrhosisMetabolic syndromeDuct obstructionLiver diseaseImmune cellsNeutrophil activationPathophysiological levelsCholangitisInflammationInjury
2019
Inflammasome Is Activated in the Liver of Cholestatic Patients and Aggravates Hepatic Injury in Bile Duct–Ligated Mouse
Cai SY, Ge M, Mennone A, Hoque R, Ouyang X, Boyer JL. Inflammasome Is Activated in the Liver of Cholestatic Patients and Aggravates Hepatic Injury in Bile Duct–Ligated Mouse. Cellular And Molecular Gastroenterology And Hepatology 2019, 9: 679-688. PMID: 31887435, PMCID: PMC7160576, DOI: 10.1016/j.jcmgh.2019.12.008.Peer-Reviewed Original ResearchConceptsWT BDL miceCholestatic liver injuryBDL liversBDL miceBile duct ligationBile acidsLiver injuryCholestatic patientsIL-1βM2 anti-inflammatory macrophagesPrimary sclerosing cholangitisPlasma IL-1βLiver hydroxyproline contentLiver of patientsPrimary biliary cholangitisHealthy control subjectsCD206-positive cellsAnti-inflammatory macrophagesIL-1β inductionEndogenous bile acidsCaspase-1 cleavageProcaspase-1 cleavageMouse hepatocytesSclerosing cholangitisLiver histology
2018
Solute Carrier Organic Anion Transporter Family Member 3A1 Is a Bile Acid Efflux Transporter in Cholestasis
Pan Q, Zhang X, Zhang L, Cheng Y, Zhao N, Li F, Zhou X, Chen S, Li J, Xu S, Huang D, Chen Y, Li L, Wang H, Chen W, Cai SY, Boyer JL, Chai J. Solute Carrier Organic Anion Transporter Family Member 3A1 Is a Bile Acid Efflux Transporter in Cholestasis. Gastroenterology 2018, 155: 1578-1592.e16. PMID: 30063921, PMCID: PMC6221191, DOI: 10.1053/j.gastro.2018.07.031.Peer-Reviewed Original ResearchConceptsBile duct ligationLiver tissueBile acidsHepatic levelsHepatoma cell lineFibroblast growth factor 19Cholestatic liver tissuesEfflux transportersCholic acid dietDevelopment of cholestasisGrowth factor 19Sprague-Dawley ratsShorter survival timeBile acid homeostasisHealthy liver tissueReal-time quantitative polymerase chain reactionNuclear factor κBCell linesQuantitative polymerase chain reactionHuman primary hepatocytesMessenger RNALiver injuryCa dietControl miceC57BL/6J mice
2017
Mechanisms of bile acid mediated inflammation in the liver
Li M, Cai SY, Boyer JL. Mechanisms of bile acid mediated inflammation in the liver. Molecular Aspects Of Medicine 2017, 56: 45-53. PMID: 28606651, PMCID: PMC5662014, DOI: 10.1016/j.mam.2017.06.001.Peer-Reviewed Original ResearchConceptsLiver injuryBile acidsCholestatic animal modelsCauses of cholestasisCholestatic liver injuryInnate immune cellsBiliary injuryNeutrophil recruitmentBile flowImmune cellsEffective therapyInflammatory responseAnimal modelsMolecular mediatorsCholestasisInjuryNovel targetLiverElevated levelsPathological processesMolecular mechanismsHepatocytesInflammationPatientsPathogenesisStudies on the mechanisms of bile acid initiated hepatic inflammation in cholestatic liver injury.
Cai SY, Boyer JL. Studies on the mechanisms of bile acid initiated hepatic inflammation in cholestatic liver injury. Inflammation And Cell Signaling 2017, 4 PMID: 28804737, PMCID: PMC5553904, DOI: 10.14800/ics.1561.Peer-Reviewed Original Research
2015
Canalicular membrane MRP2/ABCC2 internalization is determined by Ezrin Thr567 phosphorylation in human obstructive cholestasis
Chai J, Cai SY, Liu X, Lian W, Chen S, Zhang L, Feng X, Cheng Y, He X, He Y, Chen L, Wang R, Wang H, Boyer JL, Chen W. Canalicular membrane MRP2/ABCC2 internalization is determined by Ezrin Thr567 phosphorylation in human obstructive cholestasis. Journal Of Hepatology 2015, 63: 1440-1448. PMID: 26212029, PMCID: PMC4686151, DOI: 10.1016/j.jhep.2015.07.016.Peer-Reviewed Original ResearchMeSH KeywordsAdultBile CanaliculiCase-Control StudiesCholestasisCytoskeletal ProteinsFemaleGallstonesGene Knockdown TechniquesHep G2 CellsHumansLiverMaleMembrane ProteinsMiddle AgedModels, BiologicalMultidrug Resistance-Associated Protein 2Multidrug Resistance-Associated ProteinsPhosphorylationProtein Kinase CReceptors, Autocrine Motility FactorRNA, MessengerThreonineConceptsObstructive cholestasisCholestatic liverMRP2 expressionMrp2 internalizationHepG2 cellsHuman obstructive cholestasisMRP2 protein expressionMembrane expressionHepatic MRP2 expressionNon-cholestatic controlsExpression of PKCαTotal protein levelsBile ductCholestatic patientsCholestasisBile acidsPatientsAbstractTextHuman liverProtein expressionProtein levelsLiverMRP2JaundiceAIMS
2013
Biosynthesis and trafficking of the bile salt export pump, BSEP: Therapeutic implications of BSEP mutations
Soroka CJ, Boyer JL. Biosynthesis and trafficking of the bile salt export pump, BSEP: Therapeutic implications of BSEP mutations. Molecular Aspects Of Medicine 2013, 37: 3-14. PMID: 23685087, PMCID: PMC3784619, DOI: 10.1016/j.mam.2013.05.001.Peer-Reviewed Original ResearchConceptsBenign recurrent intrahepatic cholestasis type 2Progressive familial intrahepatic cholestasis type 2Cell biological aspectsBile salt export pumpTranslational regulationCell biologyMembrane transportersPrimary transporterBile salt-dependent bile flowType 2Bile acidsRate-limiting stepExport pumpDrug-induced cholestasisBiological aspectsBiosynthesisTraffickingTransportersBSEP mutationsMutationsCholestatic diseaseIntrahepatic cholestasisBile flowBiliary systemEnterohepatic circulation
2011
Ostα depletion protects liver from oral bile acid load
Soroka CJ, Velazquez H, Mennone A, Ballatori N, Boyer JL. Ostα depletion protects liver from oral bile acid load. AJP Gastrointestinal And Liver Physiology 2011, 301: g574-g579. PMID: 21719738, PMCID: PMC3174539, DOI: 10.1152/ajpgi.00141.2011.Peer-Reviewed Original ResearchConceptsExcess bile acidsCholic acid feedingWild-type miceBile acid overloadBile acidsLiver injuryAcid overloadLower serum ALT levelsIntestinal bile acid absorptionAcid feedingBile acid loadSerum ALT levelsBile acid absorptionBile acid lossBile duct ligationEffective therapeutic targetBile acid homeostasisWild-type controlsALT levelsUrinary eliminationIntestinal lossObstructive cholestasisIntestinal functionDuct ligationUrinary clearance
2010
Cholestasis: Genetic and Acquired
Boyer J. Cholestasis: Genetic and Acquired. Seminars In Liver Disease 2010, 30: 113-115. PMID: 20422493, DOI: 10.1055/s-0030-1253220.Peer-Reviewed Original ResearchConceptsBile salt export pumpCholestatic liver diseaseMultidrug resistance protein 3Cholestatic liver injuryLiver diseaseBile acidsBile salt transportersIssue of SeminarsLiver injuryCholestatic disordersBile flowSulfate conjugatesSodium taurocholate co-transporting polypeptideBile duct-cannulated animalsBile formationExport pumpProtein 3Bile acid-independent bile flowSalt transportersTaurocholate co-transporting polypeptideOrganic solute transporters alphaDependent bile salt transporterApical sodium-dependent bile salt transporterFamilial intrahepatic cholestasis-1Drug-induced cholestasis
2007
Clinical trial: modulation of human placental multidrug resistance proteins in cholestasis of pregnancy by ursodeoxycholic acid
AZZAROLI F, MENNONE A, FELETTI V, SIMONI P, BAGLIVO E, MONTAGNANI M, RIZZO N, PELUSI G, DE ALOYSIO D, LODATO F, FESTI D, COLECCHIA A, RODA E, BOYER J, MAZZELLA G. Clinical trial: modulation of human placental multidrug resistance proteins in cholestasis of pregnancy by ursodeoxycholic acid. Alimentary Pharmacology & Therapeutics 2007, 26: 1139-1146. PMID: 17894656, DOI: 10.1111/j.1365-2036.2007.03462.x.Peer-Reviewed Original ResearchConceptsUrsodeoxycholic acid administrationBile acid levelsUrsodeoxycholic acidBile acidsAcid administrationIntrahepatic cholestasisCord bloodMaternal serum bile acidsCord blood bilirubinAcid levelsRNA expressionCholestasis of pregnancySerum bile acidsTotal bile acidsMRP3 protein expressionPregnancy patientsPhysiological pregnancyPregnant womenMultidrug resistance proteinBlood bilirubinMRP2 expressionMRP4 expressionCholestasisMultidrug resistancePregnancy
2001
Cellular localization and up‐regulation of multidrug resistance–associated protein 3 in hepatocytes and cholangiocytes during obstructive cholestasis in rat liver
Soroka C, Lee J, Azzaroli F, Boyer J. Cellular localization and up‐regulation of multidrug resistance–associated protein 3 in hepatocytes and cholangiocytes during obstructive cholestasis in rat liver. Hepatology 2001, 33: 783-791. PMID: 11283840, DOI: 10.1053/jhep.2001.23501.Peer-Reviewed Original ResearchConceptsObstructive cholestasisMultidrug resistance-associated protein 3Bile duct-ligated animalsMultidrug resistanceToxic bile acidsModel of cholestasisDuct-ligated animalsExpression of MRP3Intensity of stainingHepatocytes of liverWestern blot analysisBile ductHepatic expressionCentral veinCholestasisMRP3 expressionNormal liverBile acidsPericentral regionsIndirect immunofluorescenceProtein 3Days postligationMRP3Mrp2 proteinLiver
1999
Hepatic Toxicity and Persistence of ser/thr Protein Phosphatase Inhibition by Microcystin in the Little Skate Raja erinacea
Runnegar M, Seward D, Ballatori N, Crawford J, Boyer J. Hepatic Toxicity and Persistence of ser/thr Protein Phosphatase Inhibition by Microcystin in the Little Skate Raja erinacea. Toxicology And Applied Pharmacology 1999, 161: 40-49. PMID: 10558922, DOI: 10.1006/taap.1999.8783.Peer-Reviewed Original ResearchConceptsDose-dependent inhibitionSkate hepatocytesUptake of microcystinNear complete inhibitionPP activityInflammatory changesHepatic toxicityHepatocyte necrosisHistological changesAccompanying inhibitionHepatic lesionsBile acidsHigh dosesOnly organSignificant inhibitionSkate Raja erinaceaLittle skate Raja erinaceaInhibitionLiverRectal glandBiliary bile acids in primary biliary cirrhosis: Effect of ursodeoxycholic acid
Combes B, Carithers R, Maddrey W, Munoz S, Garcia‐Tsao G, Bonner G, Boyer J, Luketic V, Shiffman M, Peters M, White H, Zetterman R, Risser R, Rossi S, Hofmann A. Biliary bile acids in primary biliary cirrhosis: Effect of ursodeoxycholic acid. Hepatology 1999, 29: 1649-1654. PMID: 10347103, PMCID: PMC4004074, DOI: 10.1002/hep.510290618.Peer-Reviewed Original ResearchMeSH KeywordsBileBile Acids and SaltsChenodeoxycholic AcidCholic AcidChromatography, GasChromatography, High Pressure LiquidDeoxycholic AcidDouble-Blind MethodDrug Administration ScheduleFemaleHumansLithocholic AcidLiver Cirrhosis, BiliaryMaleMiddle AgedPlacebosRegression AnalysisReproducibility of ResultsTime FactorsUrsodeoxycholic AcidConceptsPrimary biliary cirrhosisBile acid compositionUrsodeoxycholic acidBile acidsBiliary cirrhosisSeverity of PBCSingle bedtime dosePlacebo-controlled trialBiliary bile acidsEndogenous bile acidsMajor bile acidsBedtime dosePlacebo medicationDuodenal bileHigh-pressure liquid chromatography methodPatientsNormal personsBileSignificant decreaseCirrhosisAcid compositionCDCATaurineLiquid chromatography methodYears
1998
Endotoxin downregulates rat hepatic ntcp gene expression via decreased activity of critical transcription factors.
Trauner M, Arrese M, Lee H, Boyer J, Karpen S. Endotoxin downregulates rat hepatic ntcp gene expression via decreased activity of critical transcription factors. Journal Of Clinical Investigation 1998, 101: 2092-2100. PMID: 9593765, PMCID: PMC508797, DOI: 10.1172/jci1680.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBile Acids and SaltsCarrier ProteinsCells, CulturedCholestasisDNA-Binding ProteinsDown-RegulationEndotoxinsGene Expression RegulationHepatocyte Nuclear Factor 1Hepatocyte Nuclear Factor 1-alphaHepatocyte Nuclear Factor 1-betaLiverMaleMembrane Transport ProteinsNuclear ProteinsOrganic Anion Transporters, Sodium-DependentPromoter Regions, GeneticRatsRats, Sprague-DawleyRNA, MessengerSepsisSymportersTranscription FactorsConceptsNuclear binding activityNtcp mRNA levelsMRNA levelsHepatobiliary transportersMRNA expressionCritical transcription factorTime pointsSepsis-associated cholestasisNuclear factor-kappaBSodium-dependent uptakeEffector cytokinesSequential time pointsEndotoxin administrationPretreatment levelsBinding activityMaximal decreaseBile acidsFactor-kappaBHepatocyte nuclear factor 1Normal levelsHepatic basolateral membraneNuclear factorMarked reductionCoordinated downregulationEndotoxin
1997
Bile acid concentrations in human and rat liver tissue and in hepatocyte nuclei
Setchell K, Rodrigues C, Clerici C, Solinas A, Morelli A, Gartung C, Boyer J. Bile acid concentrations in human and rat liver tissue and in hepatocyte nuclei. Gastroenterology 1997, 112: 226-235. PMID: 8978363, DOI: 10.1016/s0016-5085(97)70239-7.Peer-Reviewed Original ResearchConceptsBile acid concentrationsBile acid administrationBile duct ligationBile acid poolLiver tissueBile acidsAcid administrationRat liver tissueDuct ligationTotal bile acid concentrationTissue concentrationsBile acid compositionSham-operated ratsLiver tissue levelsMajor bile acidsHydrophobic bile acidsHepatocyte nucleiAcid poolHuman liver tissueExperimental cholestasisAbstractTextTissue levelsRat hepatic nucleiAcid concentrationAdministration