2023
Bile Acid Induced Inflammation and the Role of β-Catenin
Boyer J. Bile Acid Induced Inflammation and the Role of β-Catenin. Cellular And Molecular Gastroenterology And Hepatology 2023, 16: 1033. PMID: 37690462, PMCID: PMC10685134, DOI: 10.1016/j.jcmgh.2023.08.009.Commentaries, Editorials and LettersOrganic 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 ResearchMeSH KeywordsAnimalsBile Acids and SaltsCholestasisHumansLiverMiceOrganic Anion TransportersUrsodeoxycholic AcidConceptsBA 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 ResearchMeSH KeywordsAnimalsBile Acids and SaltsCholestasisCholic AcidsCore Binding Factor Alpha 2 SubunitHepatocytesHumansInflammationLiverMiceSTAT3 Transcription FactorConceptsJAK/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 outcomesBile formation and secretion: An update
Boyer JL, Soroka CJ. Bile formation and secretion: An update. Journal Of Hepatology 2021, 75: 190-201. PMID: 33617926, DOI: 10.1016/j.jhep.2021.02.011.Peer-Reviewed Original Research
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 inhibitorFenofibrate 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 disease
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 ResearchMeSH KeywordsAnimalsBile Acids and SaltsCholestasisCytokinesHepatocytesHumansInflammationInflammation MediatorsLiver DiseasesMaleMiceMice, KnockoutConceptsLiver 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 areasCombination Therapy of All-Trans Retinoic Acid With Ursodeoxycholic Acid in Patients With Primary Sclerosing Cholangitis
Assis DN, Abdelghany O, Cai SY, Gossard AA, Eaton JE, Keach JC, Deng Y, Setchell KD, Ciarleglio M, Lindor KD, Boyer JL. Combination Therapy of All-Trans Retinoic Acid With Ursodeoxycholic Acid in Patients With Primary Sclerosing Cholangitis. Journal Of Clinical Gastroenterology 2017, 51: e11-e16. PMID: 27428727, PMCID: PMC5218875, DOI: 10.1097/mcg.0000000000000591.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overAlanine TransaminaseAlkaline PhosphataseBile Acids and SaltsCholagogues and CholereticsCholangitis, SclerosingCholestenonesDrug Therapy, CombinationFemaleHumansLiverLiver Function TestsMaleMiddle AgedPilot ProjectsTreatment OutcomeTretinoinUrsodeoxycholic AcidYoung AdultConceptsPrimary sclerosing cholangitisUrsodeoxycholic acidAlanine aminotransferaseUDCA monotherapyPrimary endpointSclerosing cholangitisMedian serum alanine aminotransferasePilot studyWeeks of therapyMarkers of inflammationSerum alanine aminotransferaseRetinoic acidAlkaline phosphataseAll-Trans Retinoic AcidSerum ALP levelsHuman pilot studyCombination of ATRAAddition of ATRABile acid synthesisTrans retinoic acidExploratory pilot studyALT levelsAccepted therapyWeek 12C4 levels
2013
Bile Formation and Secretion
Boyer JL. Bile Formation and Secretion. 2013, 3: 1035-1078. PMID: 23897680, PMCID: PMC4091928, DOI: 10.1002/cphy.c120027.Peer-Reviewed Original ResearchAdult sea lamprey tolerates biliary atresia by altering bile salt composition and renal excretion
Cai S, Lionarons DA, Hagey L, Soroka CJ, Mennone A, Boyer JL. Adult sea lamprey tolerates biliary atresia by altering bile salt composition and renal excretion. Hepatology 2013, 57: 2418-2426. PMID: 23175353, PMCID: PMC3604052, DOI: 10.1002/hep.26161.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBile Acids and SaltsBiliary AtresiaCholestasisDisease Models, AnimalFemaleHomeostasisKidneyLarvaLiverMaleOrganic Anion TransportersPetromyzonConceptsRenal excretionBile salt compositionBiliary atresiaBile saltsPlasma bile salt levelsEvidence of necrosisAdult liverBile salt levelsBile salt homeostasisNormal plasma levelsForms of cholestasisBile salt transportersCollection of urineAdult lampreysPredominant bile saltProgressive diseaseExogenous organic anionsBile ductPlasma levelsMajor bile saltsAnimal modelsC27 bile alcoholsCholestasisSalt transportersBile alcoholsBiosynthesis 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
Combination of retinoic acid and ursodeoxycholic acid attenuates liver injury in bile duct–ligated rats and human hepatic cells
He H, Mennone A, Boyer JL, Cai S. Combination of retinoic acid and ursodeoxycholic acid attenuates liver injury in bile duct–ligated rats and human hepatic cells. Hepatology 2010, 53: 548-557. PMID: 21274875, PMCID: PMC3069505, DOI: 10.1002/hep.24047.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBile Acids and SaltsBile DuctsCell ProliferationCells, CulturedCholestasis, IntrahepaticCholesterol 7-alpha-HydroxylaseCollagen Type ICollagen Type I, alpha 1 ChainDisease Models, AnimalHepatocytesHumansLigationLiverMaleMatrix Metalloproteinase 2RatsRats, Sprague-DawleySmad2 ProteinTretinoinUrsodeoxycholic AcidConceptsBile duct ligationBile salt pool sizeLX-2 cellsUrsodeoxycholic acidHepatic stellate cellsRetinoic acidLiver fibrosisStellate cellsPhosphate-buffered salineCommon bile duct ligationMale Sprague-Dawley ratsPrimary human hepatic stellate cellsTumor necrosis factor αBile duct-ligated ratsHuman hepatic stellate cellsBile duct proliferationHuman hepatocytesLiver hydroxyproline contentNecrosis factor αSprague-Dawley ratsAcute promyelocytic leukemiaΑ-SMA expressionDuct-ligated ratsSmooth muscle actinMatrix metalloproteinase-2The Bile Salt Export Pump: Clinical and Experimental Aspects of Genetic and Acquired Cholestatic Liver Disease
Lam P, Soroka C, Boyer J. The Bile Salt Export Pump: Clinical and Experimental Aspects of Genetic and Acquired Cholestatic Liver Disease. Seminars In Liver Disease 2010, 30: 125-133. PMID: 20422495, PMCID: PMC3008346, DOI: 10.1055/s-0030-1253222.Peer-Reviewed Original ResearchConceptsBenign recurrent intrahepatic cholestasis type 2Progressive familial intrahepatic cholestasis type 2Bile salt export pumpDrug-induced cholestasisType 2Export pumpCholestatic liver diseaseBile salt secretionForms of cholestasisDifferent genetic formsLiver diseaseCholestatic disordersIntrahepatic cholestasisBSEP expressionPathophysiologic processesBSEP deficiencyAnimal modelsCholestasisGenetic formsBile saltsSalt secretionMolecular characteristicsPivotal roleCell culturesPrimary transporter
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
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