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
Outcome of COVID‐19 in Patients With Autoimmune Hepatitis: An International Multicenter Study
Efe C, Dhanasekaran R, Lammert C, Ebik B, la Tijera F, Aloman C, Calışkan A, Peralta M, Gerussi A, Massoumi H, Catana AM, Torgutalp M, Purnak T, Rigamonti C, Aldana A, Khakoo N, Kacmaz H, Nazal L, Frager S, Demir N, Irak K, Ellik ZM, Balaban Y, Atay K, Eren F, Cristoferi L, Batıbay E, Urzua Á, Snijders R, Kıyıcı M, Akyıldız M, Ekin N, Carr RM, Harputluoğlu M, Hatemi I, Mendizabal M, Silva M, Idilman R, Silveira M, Drenth JPH, Assis DN, Björnsson E, Boyer JL, Invernizzi P, Levy C, Schiano TD, Ridruejo E, Wahlin S. Outcome of COVID‐19 in Patients With Autoimmune Hepatitis: An International Multicenter Study. Hepatology 2021, 73: 2099-2109. PMID: 33713486, PMCID: PMC8250536, DOI: 10.1002/hep.31797.Peer-Reviewed Original ResearchConceptsSevere COVID-19Chronic liver diseaseAutoimmune hepatitisLiver injuryMulticenter studyCOVID-19Causes of CLDPropensity score-matched cohortSevere COVID-19 outcomesContinuation of immunosuppressionMaintenance of immunosuppressionOutcomes of patientsIntensive care admissionUse of antiviralsInternational multicenter studyCOVID-19 outcomesCOVID-19 diagnosisContinued immunosuppressionCare admissionCause mortalityIndependent predictorsMedian ageLiver diseaseMechanical ventilationRetrospective studyThe 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
Hepatic NFAT signaling regulates the expression of inflammatory cytokines in cholestasis
Cai SY, Yu D, Soroka CJ, Wang J, Boyer JL. Hepatic NFAT signaling regulates the expression of inflammatory cytokines in cholestasis. Journal Of Hepatology 2020, 74: 550-559. PMID: 33039404, PMCID: PMC7897288, DOI: 10.1016/j.jhep.2020.09.035.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsATP Binding Cassette Transporter, Subfamily BBile Acids and SaltsCells, CulturedCholangitis, SclerosingCytokinesDisease Models, AnimalFemaleGene Expression RegulationGene Knockdown TechniquesHepatocytesHumansLiverLiver Cirrhosis, BiliaryMiceMice, Inbred C57BLMice, KnockoutNFATC Transcription FactorsPyrazolesSignal TransductionTreatment OutcomeConceptsCholestatic liver injuryLiver injuryInflammatory genesIL-8NFAT activationCholestatic liver tissuesHepatic cytokine expressionReduced liver injurySpecific NFAT inhibitorsHepatic inflammatory responseInduces liver injuryMouse hepatocytesIL-8 expressionActivated T cellsIL-8 promoterElevated tissue levelsGene reporterInflammatory cytokinesCytokine expressionElevated mRNA levelsInflammatory responseCholestatic liverT cellsImmune responseNFAT inhibitorThe 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 miceCenicriviroc, a cytokine receptor antagonist, potentiates all‐trans retinoic acid in reducing liver injury in cholestatic rodents
Yu D, Cai S, Mennone A, Vig P, Boyer JL. Cenicriviroc, a cytokine receptor antagonist, potentiates all‐trans retinoic acid in reducing liver injury in cholestatic rodents. Liver International 2018, 38: 1128-1138. PMID: 29356312, PMCID: PMC6032984, DOI: 10.1111/liv.13698.Peer-Reviewed Original ResearchConceptsBile acid pool sizeTrans retinoic acidAcid pool sizePlasma liver enzymesLiver injurySuperior therapeutic effectLiver necrosisLiver enzymesT cellsTherapeutic effectRetinoic acidAntagonist of CCR2Hepatic inflammatory cellsCholestatic liver injuryBile duct proliferationBody weight ratioCholestatic liver diseasePro-inflammatory cytokinesCytokine receptor antagonistsHepatic hydroxyproline contentExpression of cytokinesDuct-ligated ratsBile acid synthesisHepatic infiltrationLiver disease
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 mechanismsHepatocytesInflammationPatientsPathogenesisBile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory response
Cai SY, Ouyang X, Chen Y, Soroka CJ, Wang J, Mennone A, Wang Y, Mehal WZ, Jain D, Boyer JL. Bile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory response. JCI Insight 2017, 2: e90780. PMID: 28289714, PMCID: PMC5333973, DOI: 10.1172/jci.insight.90780.Peer-Reviewed Original ResearchConceptsLiver injuryInflammatory responseBile acid-induced liver injuryCholestatic liver injuryInflammatory liver injuryProinflammatory cytokine expressionCholestatic liver diseaseBile duct ligationVivo mouse modelHepatic infiltrationInflammatory injurySerum aminotransferasesLiver diseaseCholestatic patientsCytokine expressionChemokine inductionPathophysiologic concentrationsNeutrophil chemotaxisDuct ligationPathophysiologic levelsMouse modelNew therapiesInnate immunityInjuryPeriportal areasStudies 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
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
2015
Na+/H+ exchanger regulatory factor 1 knockout mice have an attenuated hepatic inflammatory response and are protected from cholestatic liver injury
Li M, Mennone A, Soroka CJ, Hagey LR, Ouyang X, Weinman EJ, Boyer JL. Na+/H+ exchanger regulatory factor 1 knockout mice have an attenuated hepatic inflammatory response and are protected from cholestatic liver injury. Hepatology 2015, 62: 1227-1236. PMID: 26108984, PMCID: PMC4589453, DOI: 10.1002/hep.27956.Peer-Reviewed Original ResearchConceptsBile duct ligationLiver injuryInflammatory responseICAM-1BDL miceBDL-induced liver injuryNeutrophil-mediated liver injuryTotal bile acid concentrationTumor necrosis factor alphaIntercellular adhesion molecule-1Hepatic neutrophil accumulationAttenuated liver injuryCholestatic liver injuryHepatic inflammatory responseMouse liverSerum alanine aminotransferaseBile acid concentrationsHepatic inflammatory diseasesICAM-1 expressionNecrosis factor alphaAdhesion molecule-1Wild-type miceICAM-1 proteinNew therapeutic targetsMessenger RNA levels
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
2006
The organic anion transport polypeptide 1d1 (Oatp1d1) mediates hepatocellular uptake of phalloidin and microcystin into skate liver
Meier-Abt F, Hammann-Hänni A, Stieger B, Ballatori N, Boyer J. The organic anion transport polypeptide 1d1 (Oatp1d1) mediates hepatocellular uptake of phalloidin and microcystin into skate liver. Toxicology And Applied Pharmacology 2006, 218: 274-279. PMID: 17198718, DOI: 10.1016/j.taap.2006.11.015.Peer-Reviewed Original ResearchConceptsSkate liverToxic liver injuryFunctional transport activityLiver-specific OATPsOrganic anion transporting polypeptidesLiver injuryOrganic anion transportersWater-injected oocytesXenobiotic toxinsHepatocellular uptakeBile saltsSkate hepatocytesOATP substratesHuman brainLiverPresent studyOatps/OATPsAnion transportersOATPDemethylphalloinHepatocytesTransport activityToxinCellular uptakeUptake
2001
Adaptive regulation of bile salt transporters in kidney and liver in obstructive cholestasis in the rat
Lee J, Azzaroli F, Wang L, Soroka C, Gigliozzi A, Setchell K, Kramer W, Boyer J. Adaptive regulation of bile salt transporters in kidney and liver in obstructive cholestasis in the rat. Gastroenterology 2001, 121: 1473-1484. PMID: 11729126, DOI: 10.1053/gast.2001.29608.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PhysiologicalAnimalsBile Acids and SaltsCarrier ProteinsCholestasisCommon Bile DuctFluorescent Antibody TechniqueKidneyLigationLiverMaleMicrovilliMitochondrial ProteinsOrganic Anion Transporters, Sodium-DependentRatsRats, Sprague-DawleyRibosomal ProteinsRNA, MessengerSaccharomyces cerevisiae ProteinsSymportersConceptsBile salt excretionCommon bile duct ligationBile salt transportersBile duct ligationSalt excretionObstructive cholestasisSalt transportersDuct ligationCommon bile duct obstructionKidney 14 daysBile duct obstructionBile salt transport proteinsSerum bile saltsBrush border membrane vesiclesProtein 2 expressionBile salt transportSodium-dependent uptakeExtrahepatic pathwaysLiver injuryDuct obstructionTissue immunofluorescenceBorder membrane vesiclesTransporter messenger RNAExtrahepatic tissuesTotal liver
1999
Cholestatic syndromes
Trauner M, Boyer J. Cholestatic syndromes. Current Opinion In Gastroenterology 1999, 15: 217-228. PMID: 17023948, DOI: 10.1097/00001574-199905000-00006.Peer-Reviewed Original ResearchCholestatic syndromeBile duct lossPathogenesis of pruritusCholestatic liver injuryPrimary biliary cirrhosisCholestasis of pregnancyCholestatic liver diseaseDrug-induced cholestasisNew treatment strategiesHepatobiliary transport systemsBiliary cirrhosisLiver injuryClinical featuresLiver diseaseTreatment strategiesDuct lossCholestasisSyndromePathogenesisImportant new studiesNew studiesImportant mechanismCholangitisCirrhosisPruritus
1997
Extrahepatic biliary obstruction impairs microvascular perfusion and increases leukocyte adhesion in rat liver
Koeppel T, Trauner M, Baas J, Thies J, Schlosser S, Post S, Gebhard M, Herfarth C, Boyer J, Otto G. Extrahepatic biliary obstruction impairs microvascular perfusion and increases leukocyte adhesion in rat liver. Hepatology 1997, 26: 1085-1091. PMID: 9362346, DOI: 10.1002/hep.510260501.Peer-Reviewed Original ResearchConceptsBile duct ligationIntravital fluorescence microscopyHepatic microvascular perfusionAcute biliary obstructionMicrovascular perfusionLeukocyte adhesionBiliary obstructionIntercellular adhesion molecule-1 protein expressionLeukocyte-endothelial cell interactionsMale Wistar ratsHydrogen gas clearanceICAM-1 expressionSham-operated controlsRat liverWestern blot analysisSinusoidal perfusionNeutrophil infiltrationLiver injuryHepatic microcirculationLiver damageLiver microcirculationTissue immunofluorescenceDuct ligationWistar ratsMarked impairment