2023
Human vascularized bile duct-on-a chip: a multi-cellular micro-physiological system for studying cholestatic liver disease
Du Y, de Jong I, Gupta K, Waisbourd-Zinman O, Har-Zahav A, Soroka C, Boyer J, Llewellyn J, Liu C, Naji A, Polacheck W, Wells R. Human vascularized bile duct-on-a chip: a multi-cellular micro-physiological system for studying cholestatic liver disease. Biofabrication 2023, 16: 015004. PMID: 37820623, PMCID: PMC10587873, DOI: 10.1088/1758-5090/ad0261.Peer-Reviewed Original ResearchMeSH KeywordsBile DuctsCholangitis, SclerosingEndothelial CellsHumansLeukocytes, MononuclearLiver DiseasesSignal TransductionConceptsCholestatic liver diseasePrimary sclerosing cholangitisLiver diseaseBile ductBile duct tissuesDuct tissuePeripheral blood mononuclear cellsEndothelial cellsBlood mononuclear cellsNormal bile duct tissuesHuman vascular endothelial cellsVascular endothelial cellsPSC patientsSclerosing cholangitisIL-17ATh17 cellsMononuclear cellsVascular channelsBiliary organoidsCholangiocyte organoidsBlood vesselsCholangiocytesDiseaseFlow of bloodTight junctions
2021
The role of the retinoid receptor, RAR/RXR heterodimer, in liver physiology
Li B, Cai SY, Boyer JL. The role of the retinoid receptor, RAR/RXR heterodimer, in liver physiology. Biochimica Et Biophysica Acta (BBA) - Molecular Basis Of Disease 2021, 1867: 166085. PMID: 33497820, PMCID: PMC11152086, DOI: 10.1016/j.bbadis.2021.166085.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsGene Expression RegulationHumansLiverProtein MultimerizationReceptors, Retinoic AcidRetinoid X ReceptorsSignal TransductionConceptsRAR/retinoid X receptorRetinoid X receptorRAR/RXR heterodimersRetinoic acid receptorsRXR heterodimersLiver physiologySpecific genesMetabolism of lipidsBiological processesDetailed signalingLiver genesEmbryo developmentFunctional roleHepatic stellate cellsCell proliferationRetinoid receptorsX receptorGenesMechanistic viewHeterodimersPhysiologyCholesterol transportAcid receptorsStellate cellsVitamin A
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 inhibitor
2019
Bile‐Derived Organoids From Patients With Primary Sclerosing Cholangitis Recapitulate Their Inflammatory Immune Profile
Soroka CJ, Assis DN, Alrabadi LS, Roberts S, Cusack L, Jaffe AB, Boyer JL. Bile‐Derived Organoids From Patients With Primary Sclerosing Cholangitis Recapitulate Their Inflammatory Immune Profile. Hepatology 2019, 70: 871-882. PMID: 30561836, DOI: 10.1002/hep.30470.Peer-Reviewed Original ResearchMeSH KeywordsAdultBileCholangiopancreatography, Endoscopic RetrogradeCholangitis, SclerosingCytokinesFemaleFluorescent Antibody TechniqueGene Expression RegulationGenome-Wide Association StudyHumansImaging, Three-DimensionalMaleMiddle AgedOrganoidsRegistriesSensitivity and SpecificitySignal TransductionStem CellsTissue Culture TechniquesConceptsPSC patientsTumor necrosis factor alphaEpithelial cellular adhesion moleculePrimary sclerosing cholangitisChemokine ligand 20End-stage diseaseEndoscopic retrograde cholangiopancreatographyHuman leukocyte antigenT cell chemoattractantNecrosis factor alphaCellular adhesion moleculesGamma-glutamyl transferaseImmune-related genesSclerosing cholangitisClinical courseImmune profileInterleukin-17AProinflammatory mediatorsRetrograde cholangiopancreatographyLeukocyte antigenAnion exchanger 2Factor alphaInflammatory stimuliEffective treatmentBiliary-like cells
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
2016
CFTR-associated ligand is a negative regulator of Mrp2 expression
Li M, Soroka CJ, Harry K, Boyer JL. CFTR-associated ligand is a negative regulator of Mrp2 expression. American Journal Of Physiology - Cell Physiology 2016, 312: c40-c46. PMID: 27834195, PMCID: PMC5283898, DOI: 10.1152/ajpcell.00100.2016.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsCarrier ProteinsCells, CulturedChlorocebus aethiopsCOS CellsDown-RegulationGene Expression RegulationGolgi Matrix ProteinsHepatocytesHumansMaleMembrane ProteinsMembrane Transport ProteinsMiceMultidrug Resistance-Associated Protein 2Multidrug Resistance-Associated ProteinsRatsRats, Sprague-DawleySignal TransductionConceptsPull-down assaysGST pull-down assaysCOOH-terminal PDZNegative regulatorCotransfected COS-7 cellsGlutathione S-transferase fusion proteinS-transferase fusion proteinATP-binding cassette (ABC) transportersTrans-Golgi networkCystic fibrosis transmembrane conductance regulatorProtein-protein interactionsExchanger regulatory factor 1Fibrosis transmembrane conductance regulatorStreptavidin pull-down assaysTransmembrane conductance regulatorCOS-7 cellsRegulatory factor 1PDZ domainCell surface expressionPosttranscriptional regulationTransmembrane proteinPlasma membraneLLC-PK1 cellsCassette transportersCOS-7
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 Research
1998
Molecular Pathogenesis of Cholestasis
Epstein F, Trauner M, Meier P, Boyer J. Molecular Pathogenesis of Cholestasis. New England Journal Of Medicine 1998, 339: 1217-1227. PMID: 9780343, DOI: 10.1056/nejm199810223391707.Peer-Reviewed Original Research
1993
Effects of tauroursodeoxycholic acid on cytosolic Ca2+ signals in isolated rat hepatocytes
Beuers U, Nathanson M, Boyer J. Effects of tauroursodeoxycholic acid on cytosolic Ca2+ signals in isolated rat hepatocytes. Gastroenterology 1993, 104: 604-612. PMID: 8425704, DOI: 10.1016/0016-5085(93)90433-d.Peer-Reviewed Original ResearchConceptsEffect of TUDCATauroursodeoxycholic acidAdministration of TUDCAIP3-independent mechanismCytosolic free calciumIP3-sensitive Ca2Trihydroxy bile acidsCholestatic disordersHepatocyte secretionTreatment periodExtracellular Ca2Bile acidsTaurolithocholic acidMumol/Rat hepatocytesFree calciumBasal levelsTransient increaseCytosolic Ca2Levels of inositolFree mediumPhysiological concentrationsIsolated rat hepatocytesHepatocytesFourfold increase