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
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 mice
2017
Bile 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 areas
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
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 liver
2000
Expression 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, MessengerSymportersConceptsBile salt export pumpBile duct ligationCommon bile duct ligationBile salt excretionDuct ligationExport pump
1998
Maternal 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 group
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 impairmentBile acid concentrations in human and rat liver tissue and in hepatocyte nuclei
Setchell K, Rodrigues C, Clerici C, Solinas A, Morelli A, Gartung C, Boyer J. Bile acid concentrations in human and rat liver tissue and in hepatocyte nuclei. Gastroenterology 1997, 112: 226-235. PMID: 8978363, DOI: 10.1016/s0016-5085(97)70239-7.Peer-Reviewed Original ResearchConceptsBile acid concentrationsBile acid administrationBile duct ligationBile acid poolLiver tissueBile acidsAcid administrationRat liver tissueDuct ligationTotal bile acid concentrationTissue concentrationsBile acid compositionSham-operated ratsLiver tissue levelsMajor bile acidsHydrophobic bile acidsHepatocyte nucleiAcid poolHuman liver tissueExperimental cholestasisAbstractTextTissue levelsRat hepatic nucleiAcid concentrationAdministration
1975
Scanning Electron Microscopy of the Rat Liver Studies of the effect of taurolithocholate and other models of cholestasis
Layden T, Schwarz J, Boyer J. Scanning Electron Microscopy of the Rat Liver Studies of the effect of taurolithocholate and other models of cholestasis. Gastroenterology 1975, 69: 724-738. PMID: 1158090, DOI: 10.1016/s0016-5085(19)32475-8.Peer-Reviewed Original ResearchConceptsModel of cholestasisBile duct ligationEstradiol treatmentDuct ligationEffect of cholestasisEffect of taurolithocholateTLC-induced cholestasisDirect toxic effectBile canaliculiLithocholate sulfateRat liver studiesCanalicular membraneLoss of microvilliNormal findingsFinger fracturesPortal veinDistinctive abnormalitiesSimultaneous infusionCholestasisSodium taurolithocholateSevere abnormalitiesSodium taurocholateInfusionTaurolithocholateLiver studies