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
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
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
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 liverCl−-dependent secretory mechanisms in isolated rat bile duct epithelial units
Singh S, Mennone A, Gigliozzi A, Fraioli F, Boyer J. Cl−-dependent secretory mechanisms in isolated rat bile duct epithelial units. AJP Gastrointestinal And Liver Physiology 2001, 281: g438-g446. PMID: 11447024, DOI: 10.1152/ajpgi.2001.281.2.g438.Peer-Reviewed Original ResearchMeSH KeywordsAmmonium ChlorideAnimalsBariumBicarbonatesBile Ducts, IntrahepaticBumetanideCarbon DioxideCarrier ProteinsCell PolarityCells, CulturedChloridesColforsinEpithelial CellsHydrogen-Ion ConcentrationIon TransportMaleModels, BiologicalRatsRats, Sprague-DawleySodiumSodium-Potassium-Chloride SymportersConceptsCO2/HCOFluid secretionCotransport activityIntrahepatic bile duct epitheliumBile duct epitheliumDependent fluid secretionHigh intracellular Cl(-) concentrationIntracellular Cl- concentrationBile duct unitsApical Cl(-) secretionNH entryInitial acidification rateIntracellular cAMP concentrationNH4Cl exposureDuct epitheliumInhibitor bumetanideChannel inhibitorsCl(-) secretionCanalicular bileDuct unitsSecretionDependent secretionSecretory mechanismBumetanideForskolinCellular 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 mannerATP-dependent GSH and glutathioneS-conjugate transport in skate liver: role of an Mrp functional homologue
Rebbeor J, Connolly G, Henson J, Boyer J, Ballatori N. ATP-dependent GSH and glutathioneS-conjugate transport in skate liver: role of an Mrp functional homologue. AJP Gastrointestinal And Liver Physiology 2000, 279: g417-g425. PMID: 10915652, DOI: 10.1152/ajpgi.2000.279.2.g417.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsAnion Transport ProteinsAnionsATP-Binding Cassette TransportersBileBiological TransportCarrier ProteinsCell MembraneEnzyme InhibitorsGlutathioneLiverMaleOxidation-ReductionProtein BindingRatsRats, Sprague-DawleySkates, FishSubstrate SpecificityTaurocholic AcidTritiumConceptsATP-dependent transportLiver membrane vesiclesATP-dependent GSH transportMembrane vesiclesTransport activityATP-independent mechanismGlutathione-conjugate transportFunctional homologueMammalian cellsDNP-SG uptakePlasma membraneHomologous proteinsSkate liverGSH transportLow-affinity pathwayLittle skateMRP familyMultidrug resistance-associated protein 1GSH effluxFunctional assaysProtein 1First direct evidenceProtein bandsDirect evidenceHomologuesExpression 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
Carrier-mediated uptake of lucifer yellow in skate and rat hepatocytes: a fluid-phase marker revisited
Ballatori N, Hager D, Nundy S, Miller D, Boyer J. Carrier-mediated uptake of lucifer yellow in skate and rat hepatocytes: a fluid-phase marker revisited. American Journal Of Physiology 1999, 277: g896-g904. PMID: 10516157, DOI: 10.1152/ajpgi.1999.277.4.g896.Peer-Reviewed Original ResearchVasoactive 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-arginineIntracellular pH regulation in bombesin-stimulated secretion in isolated bile duct units from rat liver
Cho W, Mennone A, Boyer J. Intracellular pH regulation in bombesin-stimulated secretion in isolated bile duct units from rat liver. American Journal Of Physiology 1998, 275: g1028-g1036. PMID: 9815033, DOI: 10.1152/ajpgi.1998.275.5.g1028.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntiportersBicarbonatesBile Ducts, IntrahepaticBombesinCarrier ProteinsChloride-Bicarbonate AntiportersChloridesFluoresceinsFluorescent DyesHEPESHydrogen-Ion ConcentrationIn Vitro TechniquesMaleModels, BiologicalRatsRats, Sprague-DawleySodiumSodium-Bicarbonate SymportersSodium-Hydrogen ExchangersConceptsHCO-3 secretionBile duct unitsDuct unitsAcid-extruding mechanismsEffect of bombesinRat liverCl-/HCOBombesin-stimulated secretionRegulation of intracellularBiliary secretionNormal rat liverBombesinCholangiocytesSecretionUnderlying mechanismLiverBasalPH regulationCounterregulatoryNeuropeptidesExchange activityActivityMaternal cholestasis does not affect the ontogenic pattern of expression of the Na+/Taurocholate cotransporting polypeptide (ntcp) in the fetal and neonatal rat liver
Arrese M, Trauner M, Ananthanarayanan M, Boyer J, Suchy F. Maternal cholestasis does not affect the ontogenic pattern of expression of the Na+/Taurocholate cotransporting polypeptide (ntcp) in the fetal and neonatal rat liver. Hepatology 1998, 28: 789-795. PMID: 9731574, DOI: 10.1002/hep.510280328.Peer-Reviewed Original ResearchConceptsBile duct ligationWeeks of ageBile acid transporterFetal lifeCommon bile duct ligationOntogenic patternMaternal obstructive cholestasisBile acid excretionMRNA levelsEffect of cholestasisSham-operated animalsSteady-state mRNA levelsFunction of NTCPAcid transportersNeonatal rat liverPostnatal time pointsDays of ageMaternal cholestasisBasolateral bile acid transportersPregnant ratsCholestatic ratsLiver weightObstructive cholestasisDuct ligationMC groupEndotoxin 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 downregulationEndotoxinCyclic AMP stimulates sorting of the canalicular organic anion transporter (Mrp2/cMoat) to the apical domain in hepatocyte couplets
Roelofsen H, Soroka C, Keppler D, Boyer J. Cyclic AMP stimulates sorting of the canalicular organic anion transporter (Mrp2/cMoat) to the apical domain in hepatocyte couplets. Journal Of Cell Science 1998, 111: 1137-1145. PMID: 9512509, DOI: 10.1242/jcs.111.8.1137.Peer-Reviewed Original ResearchConceptsTransport proteinsApical membraneApical domainTransporter-containing vesiclesMultidrug resistance protein 2Protein 2Cell-cell contactMicrotubule-dependent fashionBasolateral plasma membraneApical proteinsEffect of cAMPVesicle trafficAnion transportersSecretory polarityOrganic anion transportersPlasma membraneCanalicular membraneAnion transport capacityTransport activityApical excretionApical poleCanalicular organic anion transportMultispecific organic anion transporterAmphiphilic organic anionsTransport function
1997
The rat canalicular conjugate export pump (Mrp2) is down-regulated in intrahepatic and obstructive cholestasis
Trauner M, Arrese M, Soroka C, Ananthanarayanan M, Koeppel T, Schlosser S, Suchy F, Keppler D, Boyer J. The rat canalicular conjugate export pump (Mrp2) is down-regulated in intrahepatic and obstructive cholestasis. Gastroenterology 1997, 113: 255-264. PMID: 9207286, DOI: 10.1016/s0016-5085(97)70103-3.Peer-Reviewed Original ResearchAnimalsATP-Binding Cassette TransportersBile CanaliculiBlotting, NorthernBlotting, WesternCholestasisCholestasis, IntrahepaticCommon Bile DuctDown-RegulationDrug Resistance, MultipleEthinyl EstradiolFluorescent Antibody Technique, IndirectGene Expression RegulationLipopolysaccharidesMaleMultidrug Resistance-Associated ProteinsRatsRats, Sprague-DawleyRNA, Messenger