2019
Pathophysiology of Cystic Fibrosis Liver Disease: A Channelopathy Leading to Alterations in Innate Immunity and in Microbiota
Fiorotto R, Strazzabosco M. Pathophysiology of Cystic Fibrosis Liver Disease: A Channelopathy Leading to Alterations in Innate Immunity and in Microbiota. Cellular And Molecular Gastroenterology And Hepatology 2019, 8: 197-207. PMID: 31075352, PMCID: PMC6664222, DOI: 10.1016/j.jcmgh.2019.04.013.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCF-associated liver diseaseLiver diseaseCystic fibrosisInnate immunityCystic fibrosis liver diseaseEpithelial innate immunityCystic fibrosis transmembrane conductance regulatorFibrosis transmembrane conductance regulatorNonpulmonary causesCF adultsTransmembrane conductance regulatorLiver complicationsMutations of CFTRPediatric populationAltered microbiotaIntestinal diseaseBile secretionCF mortalityDiseaseNew drugsConductance regulatorPotential targetLife expectancyBasic defectPathophysiology
2016
The cystic fibrosis transmembrane conductance regulator controls biliary epithelial inflammation and permeability by regulating Src tyrosine kinase activity
Fiorotto R, Villani A, Kourtidis A, Scirpo R, Amenduni M, Geibel PJ, Cadamuro M, Spirli C, Anastasiadis PZ, Strazzabosco M. The cystic fibrosis transmembrane conductance regulator controls biliary epithelial inflammation and permeability by regulating Src tyrosine kinase activity. Hepatology 2016, 64: 2118-2134. PMID: 27629435, PMCID: PMC5115965, DOI: 10.1002/hep.28817.Peer-Reviewed Original ResearchConceptsBiliary epithelial cellsLiver diseaseToll-like receptor 4 activityToll-like receptor 4 responsesCystic fibrosis transmembrane conductance regulatorToll-like receptor 4Nuclear factorEpithelial cellsProinflammatory cytokine productionNovel therapeutic targetEpithelial barrier functionActivated B cellsFibrosis transmembrane conductance regulatorTransmembrane conductance regulatorCytokine productionEpithelial inflammationInflammatory cellsInflammatory processReceptor 4Biliary damageInflammatory responseInflammatory cholangiopathyProtective effectBile secretionImmune pathways
2013
Bile Formation and Secretion
Boyer J. Bile Formation and Secretion. Comprehensive Physiology 2013, 3: 1035-1078. DOI: 10.1002/j.2040-4603.2013.tb00519.x.Peer-Reviewed Original ResearchApical membraneBile ductDirection of portal blood flowBile secretory unitBile secretionBile salt-dependentDeterminants of bile secretionSignal transduction pathwaysPortal blood flowCanalicular bile secretionCanals of HeringBile duct epitheliumSalt dependenceCholangiocyte secretionExport pumpTransduction pathwaysTight junctionsDuct epitheliumAnimal modelsBile canalicular lumenGenetic mutationsAqueous secretionTransport proteinsBlood flowCanalicular lumen
2012
Nuclear factor-E2-related factor 2 is a major determinant of bile acid homeostasis in the liver and intestine
Weerachayaphorn J, Mennone A, Soroka CJ, Harry K, Hagey LR, Kensler TW, Boyer JL. Nuclear factor-E2-related factor 2 is a major determinant of bile acid homeostasis in the liver and intestine. AJP Gastrointestinal And Liver Physiology 2012, 302: g925-g936. PMID: 22345550, PMCID: PMC3362073, DOI: 10.1152/ajpgi.00263.2011.Peer-Reviewed Original ResearchConceptsBile duct ligationBile acid homeostasisBile acid synthesisBile acidsLiver injuryAcid homeostasisMRNA expressionWild-type control miceBile acid transporter expressionCYP3A11 mRNA expressionBile salt export pumpBiliary bile acidsDeletion of Nrf2Bile acid reabsorptionRole of Nrf2Factor 2Bile acid hydroxylationPregnane X receptorBDL miceExpression of regulatorsControl miceDuct ligationNrf2 resultsBile secretionHepatobiliary transporters
2011
Dual farnesoid X receptor/TGR5 agonist INT‐767 reduces liver injury in the Mdr2−/− (Abcb4−/−) mouse cholangiopathy model by promoting biliary HCO output
Baghdasaryan A, Claudel T, Gumhold J, Silbert D, Adorini L, Roda A, Vecchiotti S, Gonzalez FJ, Schoonjans K, Strazzabosco M, Fickert P, Trauner M. Dual farnesoid X receptor/TGR5 agonist INT‐767 reduces liver injury in the Mdr2−/− (Abcb4−/−) mouse cholangiopathy model by promoting biliary HCO output. Hepatology 2011, 54: 1303-1312. PMID: 22006858, PMCID: PMC3744065, DOI: 10.1002/hep.24537.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphatasesAnalysis of VarianceAnimalsAnion Transport ProteinsATP Binding Cassette Transporter, Subfamily BBile Acids and SaltsBiliary Tract DiseasesCholic AcidsDisease Models, AnimalLiver DiseasesMaleMiceMice, Inbred C57BLRandom AllocationReceptors, Cytoplasmic and NuclearReceptors, G-Protein-CoupledStatistics, NonparametricConceptsFarnesoid X receptorINT-767Liver injuryChronic cholangiopathiesTGR5 agonistsINT-747Hepatic inflammationINT-777Bile secretionBiliary bile acid outputActivation of FXRNuclear farnesoid X receptorSerum liver enzymesBile acid outputBile acid homeostasisFXR-dependent mannerBile acid synthesisMembrane G protein-coupled receptorsG protein-coupled receptorsLiver transplantationProtein-coupled receptorsBiliary fibrosisAcid outputChow dietTherapeutic options
2001
Polarized expression and function of P2Y ATP receptors in rat bile duct epithelia
Dranoff J, Masyuk A, Kruglov E, LaRusso N, Nathanson M. Polarized expression and function of P2Y ATP receptors in rat bile duct epithelia. AJP Gastrointestinal And Liver Physiology 2001, 281: g1059-g1067. PMID: 11557527, DOI: 10.1152/ajpgi.2001.281.4.g1059.Peer-Reviewed Original ResearchConceptsP2Y receptor subtypesP2Y receptorsReceptor subtypesIntrahepatic bile duct unitsATP receptorsBile duct epitheliumMultiple P2Y receptor subtypesRat bile duct epitheliaBile duct unitsImportant regulatorLuminal ATPLuminal perfusionMolecular subtypesBile secretionDuct epitheliumBasolateral additionExtracellular nucleotidesDuctular secretionSubtypesCytosolic Ca2Duct unitsRT-PCRCholangiocytesReceptorsSecretionCholestatic syndromes
Trauner M, Boyer J. Cholestatic syndromes. Current Opinion In Gastroenterology 2001, 17: 242-256. PMID: 17031165, DOI: 10.1097/00001574-200105000-00007.Peer-Reviewed Original ResearchCholestatic syndromeTotal parenteral nutrition-induced cholestasisParenteral nutrition-induced cholestasisHereditary cholestatic syndromesPrimary biliary cirrhosisCholestasis of pregnancyCholestatic liver diseaseDrug-induced cholestasisHepatobiliary transport proteinsBiliary cirrhosisClinical featuresLiver diseaseBile secretionCholestasisSyndromePathogenesisImportant new studiesNew studiesCholangitisCirrhosisPregnancyDiseaseSecretionTransporter gene
2000
Cholestatic syndromes
Trauner M, Boyer J. Cholestatic syndromes. Current Opinion In Gastroenterology 2000, 16: 239-250. PMID: 17023881, DOI: 10.1097/00001574-200005000-00006.Peer-Reviewed Original Research
1999
Vasoactive 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 outputAbstractText
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-arginine
1997
Bombesin stimulates bicarbonate secretion from rat cholangiocytes: Implications for neural regulation of bile secretion
Cho W, Mennone A, Rydberg, Boyer J. Bombesin stimulates bicarbonate secretion from rat cholangiocytes: Implications for neural regulation of bile secretion. Gastroenterology 1997, 113: 311-321. PMID: 9207292, DOI: 10.1016/s0016-5085(97)70109-4.Peer-Reviewed Original ResearchConceptsBile secretionBicarbonate secretionRat liverBile duct-ligated ratsRole of bombesinHepatocyte coupletsEffect of bombesinDose-dependent increaseDuct-ligated ratsBile duct unitsCanalicular bile secretionBile pHSite of actionBile flowSubstance PReceptor inhibitorsNeural regulationAbstractTextBombesinBiliary transportDuct unitsSecretionLiverLuminal pHRat cholangiocytesIntercellular Calcium Signaling in Liver
Nathanson M, Fallon M, Burgstahler A, Mennone A, Schlosser S, Gonzalez C, Sáez J. Intercellular Calcium Signaling in Liver. Series Of The Centro De Estudios Científicos 1997, 469-481. DOI: 10.1007/978-1-4899-1795-9_27.Peer-Reviewed Original ResearchGap junctionsGap junction expressionIntercellular calcium signalingDiverse cell functionsExcitable cell typesBile secretionIsolated cell systemImportant second messengerJunction expressionCytosolic Ca2Experimental modelHormonal stimulationCell functionPhysiological circumstancesCalcium signalingIntercellular signalingHepatocytesSecond messengerOrgan-level responsesPreliminary evidenceLiverCell typesCai2Inositol 1Signaling
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 secretion
1992
Effects of Ca2+ agonists on cytosolic Ca2+ in isolated hepatocytes and on bile secretion in the isolated perfused rat liver
Nathanson M, Gautam A, Bruck R, Isales C, Boyer J. Effects of Ca2+ agonists on cytosolic Ca2+ in isolated hepatocytes and on bile secretion in the isolated perfused rat liver. Hepatology 1992, 15: 107-116. PMID: 1727785, DOI: 10.1002/hep.1840150119.Peer-Reviewed Original ResearchConceptsBile flowPerfusion pressureBile secretionCytosolic Ca2Rat liverProtein kinase CIonophore-induced increaseBromo-A23187Hepatic vasoconstrictionVasodilator papaverineProtein kinase C inhibitor HExtracellular Ca2Kinase CSecretionLiverVasopressinAgonist vasopressinBenzohydroquinoneEffect of Ca2HepatocytesActivate protein kinase CInhibitor HTwo-thirdsIsolated hepatocytesSensitive photoprotein aequorin
1989
Protein kinase C agonists inhibit bile secretion independently of effects on the microcirculation in the isolated perfused rat liver
Corasanti J, Smith N, Gordon E, Boyer J. Protein kinase C agonists inhibit bile secretion independently of effects on the microcirculation in the isolated perfused rat liver. Hepatology 1989, 10: 8-13. PMID: 2737605, DOI: 10.1002/hep.1840100103.Peer-Reviewed Original ResearchConceptsBile flowPerfusion pressureBile secretionVehicle dimethyl sulfoxideReversible decreaseConstant perfusate flowPhorbol dibutyrateVenous effluent concentrationsInactive phorbol ester 4Rat liver systemVascular redistributionHepatic microvasculaturePhorbol esterPhorbol ester 4Vasoactive agentsRole of hormonesPerfusate flowTrypan blue dyeAntagonist HProtein kinase C agonistsGm liverActive phorbol estersLiver systemRat liverOxygen consumptionVoltage-driven, taurocholate-dependent secretion in isolated hepatocyte couplets
Weinman S, Graf J, Boyer J. Voltage-driven, taurocholate-dependent secretion in isolated hepatocyte couplets. American Journal Of Physiology 1989, 256: g826-g832. PMID: 2719107, DOI: 10.1152/ajpgi.1989.256.5.g826.Peer-Reviewed Original ResearchConceptsBile secretionBile acidsSecretion rateFluid secretionIntracellular current injectionCanalicular areaHepatocyte coupletsMembrane potentialRat hepatocyte coupletsAbsence of taurocholateMicroM taurocholateFluid secretion rateBile formationSecretionCarrier-mediated transportTaurocholateLiverIntracellular voltage
1987
Mechanisms of Bile Secretion and Hepatic Transport
Boyer J. Mechanisms of Bile Secretion and Hepatic Transport. 1987, 225-252. DOI: 10.1007/978-1-4684-5404-8_12.Peer-Reviewed Original Research
1986
Mechanisms of Bile Secretion and Hepatic Transport
Boyer J. Mechanisms of Bile Secretion and Hepatic Transport. 1986, 609-636. DOI: 10.1007/978-1-4613-2097-5_35.Peer-Reviewed Original Research
1982
Hemodynamic effects on oxygen consumption and bile flow in isolated skate liver
Reed J, Smith N, Boyer J. Hemodynamic effects on oxygen consumption and bile flow in isolated skate liver. American Journal Of Physiology 1982, 242: g313-g318. PMID: 7065253, DOI: 10.1152/ajpgi.1982.242.4.g313.Peer-Reviewed Original ResearchConceptsPerfusion pressureBile flowSkate liverOxygen consumptionOrganic anion clearanceBile flow ratePortal vein pressurePerfusion of liversHemodynamic effectsVein pressureBile secretionFractional disappearance rateHepatic clearanceLiverDisappearance rateRinger's solutionPerfusionBileClearanceTaurocholateRaja erinaceaSulfobromophthaleinVivoMammalian speciesPerfusate
1979
Effect of chlorpromazine on hepatic perfusion and bile secretory function in the isolated perfused rat liver.
Tavoloni N, Reed J, Hruban Z, Boyer J. Effect of chlorpromazine on hepatic perfusion and bile secretory function in the isolated perfused rat liver. Translational Research 1979, 94: 726-41. PMID: 227976.Peer-Reviewed Original ResearchConceptsHepatic perfusionPerfusate flowBile secretionBile acid-independent bile secretionSecretory functionBile acid excretionBile secretory functionRat liverEffect of chlorpromazineLiver 20 minLobar distributionHepatic lobeAcid excretionBaseline valuesPerfusate concentrationConstant infusionHepatic ultrastructureBile acidsControl valuesCPZSodium taurocholateLiverPerfusionGM-1Liver plasma membranes
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