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 ResearchConceptsCholestatic 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
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 histologyPatient-Derived Organoids from Human Bile: An In Vitro Method to Study Cholangiopathies
Soroka CJ, Assis DN, Boyer JL. Patient-Derived Organoids from Human Bile: An In Vitro Method to Study Cholangiopathies. Methods In Molecular Biology 2019, 1981: 363-372. PMID: 31016667, DOI: 10.1007/978-1-4939-9420-5_24.BooksConceptsPrimary sclerosing cholangitisPrimary sclerosing cholangitis patientsEndoscopic retrograde cholangiopancreatographySclerosing cholangitisCholangitis patientsRetrograde cholangiopancreatographyExtrahepatic bile duct epitheliumTherapeutic endoscopic retrograde cholangiopancreatographyChemo/cytokinesEnd-stage diseaseBile duct epitheliumPatient-derived organoidsPharmacotherapeutic treatmentClinical indicationsIndividual patientsInflammatory stimuliHeterogeneous diseaseBiliary phenotypeDuct epitheliumDisease statusCholangitisCholangiopathyHuman bileBiliary cellsPatients
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
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-2
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 proteinLiverRole of sodium/hydrogen exchanger isoform NHE3 in fluid secretion and absorption in mouse and rat cholangiocytes
Mennone A, Biemesderfer D, Negoianu D, Yang C, Abbiati T, Schultheis P, Shull G, Aronson P, Boyer J. Role of sodium/hydrogen exchanger isoform NHE3 in fluid secretion and absorption in mouse and rat cholangiocytes. AJP Gastrointestinal And Liver Physiology 2001, 280: g247-g254. PMID: 11208547, DOI: 10.1152/ajpgi.2001.280.2.g247.Peer-Reviewed Original Research
2000
Molecular identification and functional characterization of Mdr1a in rat cholangiocytes
Gigliozzi A, Fraioli F, Sundaram P, Lee J, Mennone A, Alvaro D, Boyer J. Molecular identification and functional characterization of Mdr1a in rat cholangiocytes. Gastroenterology 2000, 119: 1113-1122. PMID: 11040198, DOI: 10.1053/gast.2000.18156.Peer-Reviewed Original ResearchMeSH KeywordsAcridinesAnimalsATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1ATP-Binding Cassette TransportersBile DuctsCell DivisionCell MembraneCytosolDrug Resistance, MultipleIn Vitro TechniquesIsoquinolinesKineticsMaleMicroscopy, ConfocalRatsRats, Sprague-DawleyReverse Transcriptase Polymerase Chain ReactionRhodamine 123RNA, MessengerTetrahydroisoquinolinesTranscription, GeneticVanadatesVerapamilConceptsCholangiocyte cell linePlasma membrane proteinsRat cholangiocyte cell lineCell linesCytosolic domainMembrane proteinsRhodamine 123Functional characterizationGene productsRNA transcriptsMolecular identificationMembrane subfractionsPair fragmentWestern blot analysisWestern analysisApical membraneFunctional assaysFunctional evidenceBlot analysisConfocal microscopyP-glycoprotein inhibitor verapamilRat cholangiocytesLipophilic xenobioticsReverse transcription-polymerase chain reactionDose-dependent mannerExpression of the bile salt export pump is maintained after chronic cholestasis in the rat
Lee J, Trauner M, Soroka C, Stieger B, Meier P, Boyer J. Expression of the bile salt export pump is maintained after chronic cholestasis in the rat. Gastroenterology 2000, 118: 163-172. PMID: 10611165, DOI: 10.1016/s0016-5085(00)70425-2.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsATP Binding Cassette Transporter, Subfamily B, Member 1ATP Binding Cassette Transporter, Subfamily B, Member 11ATP-Binding Cassette TransportersBile Acids and SaltsBile DuctsCarrier ProteinsCholestasisChronic DiseaseDrug Resistance, MultipleEthinyl EstradiolLigationLipopolysaccharidesMembrane ProteinsMultidrug Resistance-Associated ProteinsOrganic Anion Transporters, Sodium-DependentRatsRats, Sprague-DawleyRNA, MessengerSymporters
1999
The effect of ursodeoxycholic acid on the florid duct lesion of primary biliary cirrhosis
Combes B, Markin R, Wheeler D, Rubin R, West A, Mills A, Eigenbrodt E, Maddrey W, Munoz S, Garcia‐Tsao G, Bonner G, Boyer J, Luketic V, Shiffman M, Peters M, White H, Zetterman R, Carithers R. The effect of ursodeoxycholic acid on the florid duct lesion of primary biliary cirrhosis. Hepatology 1999, 30: 602-605. PMID: 10462363, PMCID: PMC3935822, DOI: 10.1002/hep.510300315.Peer-Reviewed Original ResearchConceptsFlorid duct lesionsPrimary biliary cirrhosisBile duct destructionDuct lesionsUrsodeoxycholic acidDuct destructionBiliary cirrhosisPlacebo-controlled trialNeedle biopsy specimensUDCA patientsAdvanced diseasePlacebo medicationEarly diseaseBiopsy specimensPatientsLesionsBeneficial effectsPathology literaturePrevalenceCirrhosisPlaceboMedicationsDiseaseYearsHepatopathologistVasoactive intestinal polypeptide is a potent regulator of bile secretion from rat cholangiocytes
Cho W, Boyer J. Vasoactive intestinal polypeptide is a potent regulator of bile secretion from rat cholangiocytes. Gastroenterology 1999, 117: 420-428. PMID: 10419925, DOI: 10.1053/gast.1999.0029900420.Peer-Reviewed Original ResearchConceptsBile duct unitsEffect of VIPBile flowBile secretionDuct unitsIntestinal polypeptideFluid secretionBile duct-ligated ratsBile salt outputVasoactive intestinal polypeptideHepatocyte coupletsDose-dependent increaseDuct-ligated ratsBile pHVIP antagonistSite of actionSubstance PSecretory responseVIP responsesReceptor inhibitorsCAMP-independent pathwayBicarbonate secretionPotent stimulantSalt outputAbstractTextCharacterization of ion transport mechanisms involved in bombesin-stimulated biliary secretion in rat cholangiocytes
Cho W, Boyer J. Characterization of ion transport mechanisms involved in bombesin-stimulated biliary secretion in rat cholangiocytes. Journal Of Hepatology 1999, 30: 1045-1051. PMID: 10406182, DOI: 10.1016/s0168-8278(99)80258-x.Peer-Reviewed Original ResearchMeSH Keywords4,4'-Diisothiocyanostilbene-2,2'-Disulfonic AcidAcetazolamideAnimalsBarium CompoundsBileBile DuctsBombesinCarbonic Anhydrase InhibitorsChloride ChannelsChloridesIn Vitro TechniquesIon TransportMaleMicroscopy, VideoNitrobenzoatesPotassium ChannelsRatsRats, Sprague-DawleyTetraethylammonium
1998
Nitric oxide and guanosine 3′,5′‐cyclic monophosphate stimulate bile secretion in isolated rat hepatocyte couplets, but not in isolated bile duct units
Trauner M, Mennone A, Gigliozzi A, Fraioli F, Boyer J. Nitric oxide and guanosine 3′,5′‐cyclic monophosphate stimulate bile secretion in isolated rat hepatocyte couplets, but not in isolated bile duct units. Hepatology 1998, 28: 1621-1628. PMID: 9828227, DOI: 10.1002/hep.510280623.Peer-Reviewed Original ResearchConceptsDuctular bile secretionBile secretionBile duct unitsNitric oxideRat hepatocyte coupletsExchanger activityNO synthesisCl-/HCO3Bile acid-independent bile flowCell-permeant cGMP analogDuct unitsEndogenous NO synthesisHepatocyte coupletsEffect of NOCell-permeant cAMP analogsLevel of hepatocytesCyclic monophosphateHepatic NO synthesisRemoval of HCO3Canalicular bile secretionNG-monomethylBile flowCholeretic effectDuctular luminaL-arginineMolecular 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 ResearchRole of glutathione in hepatic bile formation during reperfusion after cold ischemia of the rat liver
Koeppel T, Trauner M, Albert M, Arrese M, Rios-Velez L, Boyer J. Role of glutathione in hepatic bile formation during reperfusion after cold ischemia of the rat liver. Journal Of Hepatology 1998, 28: 812-819. PMID: 9625316, DOI: 10.1016/s0168-8278(98)80231-6.Peer-Reviewed Original ResearchConceptsBiliary glutathione excretionBile duct injuryCold ischemiaBile flowHepatic bile formationDuct injuryLiver transplantationBiliary tractBiliary excretionRat liverGlutathione excretionBasal bile flow ratesBile formationBile acid-independent bile flowOxidative stressLate reperfusion periodBile duct damageBile flow rateOnset of reperfusionIndependent bile flowBile duct morphologyBiliary glutathione concentrationsWistar rat liverLiver reperfusionDuct damage
1996
Bile secretion-models, mechanisms, and malfunctions. A perspective on the development of modern cellular and molecular concepts of bile secretion and cholestasis
Boyer J. Bile secretion-models, mechanisms, and malfunctions. A perspective on the development of modern cellular and molecular concepts of bile secretion and cholestasis. Journal Of Gastroenterology 1996, 31: 475-481. PMID: 8726846, DOI: 10.1007/bf02355044.Peer-Reviewed Original ResearchConceptsBile secretionBile duct epithelium: frontiers in transport physiology
Boyer J. Bile duct epithelium: frontiers in transport physiology. American Journal Of Physiology 1996, 270: g1-g5. PMID: 8772494, DOI: 10.1152/ajpgi.1996.270.1.g1.Peer-Reviewed Original Research
1995
Isolation of small polarized bile duct units.
Mennone A, Alvaro D, Cho W, Boyer J. Isolation of small polarized bile duct units. Proceedings Of The National Academy Of Sciences Of The United States Of America 1995, 92: 6527-6531. PMID: 7541542, PMCID: PMC41551, DOI: 10.1073/pnas.92.14.6527.Peer-Reviewed Original ResearchMeSH Keywords1-Methyl-3-isobutylxanthine4,4'-Diisothiocyanostilbene-2,2'-Disulfonic AcidAnimalsBicarbonatesBile DuctsBucladesineChloridesCholestasisColforsinFluoresceinsGluconatesHydrogen-Ion ConcentrationKineticsLiverMaleMicroscopy, ElectronMicroscopy, VideoRatsRats, Sprague-DawleySecretinTime FactorsConceptsBile duct unitsInterlobular bile ductsBile ductDuct unitsSmall interlobular bile ductsBile duct syndromeBile duct segmentsCholestatic liver disordersCl-/HCO3- exchange activityRat liverLiver disordersPrimary siteForskolin administrationMicroM forskolinDextran 40Duct segmentsDibutyryl cAMPUseful preparationLiverSecretionForskolinImaging techniquesDuctLuminal spaceSyndrome
1993
Effect of ursodeoxycholic acid on intracellular pH regulation in isolated rat bile duct epithelial cells
Alvaro D, Mennone A, Boyer J. Effect of ursodeoxycholic acid on intracellular pH regulation in isolated rat bile duct epithelial cells. American Journal Of Physiology 1993, 265: g783-g791. PMID: 8238362, DOI: 10.1152/ajpgi.1993.265.4.g783.Peer-Reviewed Original ResearchConceptsBile duct epithelial cellsUrsodeoxycholic acidDuct epithelial cellsBDE cellsHCO3- excretionEffect of UDCAEpithelial cellsHCO3- exchangeCholic acidKrebs-Ringer bicarbonateUDCA infusionUDCA withdrawalRat bile duct epithelial cellsKRB mediumHCO3- symportNormal rat liverIntracellular pH regulationHCO3- secretionSodium tauroursodeoxycholateSecondary activationBasal levelsPresence of HCO3TauroursodeoxycholateRat liverHypercholeresisEffect of secretion on intracellular pH regulation in isolated rat bile duct epithelial cells.
Alvaro D, Cho W, Mennone A, Boyer J. Effect of secretion on intracellular pH regulation in isolated rat bile duct epithelial cells. Journal Of Clinical Investigation 1993, 92: 1314-1325. PMID: 8397224, PMCID: PMC288273, DOI: 10.1172/jci116705.Peer-Reviewed Original ResearchConceptsBile duct epithelial cellsDuct epithelial cellsCl-/HCO3Cell depolarizationEpithelial cellsEffect of secretinCl- channel blockerEffects of secretionsCl removalCl- channel activationRat bile duct epithelial cellsKRB mediumMaximal rateRegulation of intracellularBicarbonate secretionNormal rat liverIntracellular pH regulationMM DIDSHCO3- excretionAcid loadBDE cellsSecretinMicrofluorimetric methodRat liverHCO3- influx