2018
Junctional adhesion molecules JAM-B and JAM-C promote autoimmune-mediated liver fibrosis in mice
Hintermann E, Bayer M, Conti CB, Fuchs S, Fausther M, Leung PS, Aurrand-Lions M, Taubert R, Pfeilschifter JM, Friedrich-Rust M, Schuppan D, Dranoff JA, Gershwin ME, Manns MP, Imhof BA, Christen U. Junctional adhesion molecules JAM-B and JAM-C promote autoimmune-mediated liver fibrosis in mice. Journal Of Autoimmunity 2018, 91: 83-96. PMID: 29753567, DOI: 10.1016/j.jaut.2018.05.001.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell AdhesionCell Adhesion MoleculesCells, CulturedCholangitis, SclerosingDisease Models, AnimalEndothelial CellsFatty Acids, MonounsaturatedFemaleFibrosisHepatitis, AutoimmuneHumansImmunoglobulinsInflammationLiverLiver Cirrhosis, BiliaryMiceMice, Inbred C57BLMice, KnockoutMyocytes, Smooth MuscleMyofibroblastsVascular RemodelingVasoconstrictionConceptsPrimary sclerosing cholangitisHepatic stellate cellsPrimary biliary cholangitisPortal fibroblastsJunctional adhesion molecule JAMEndothelial cellsLiver fibrosisBile duct stricturesChronic liver diseaseAnti-fibrosis therapyBiopsies of patientsLoss of JAMRole of JAMSmooth muscle cellsEndothelial JAMIntrahepatic vasoconstrictionFunction of JAMSclerosing cholangitisDuct stricturesLiver inflammationBiliary cholangitisBiliary fibrosisChronic modelLeukocyte infiltrationLiver disease
2017
Liver myofibroblasts of murine origins express mesothelin: Identification of novel rat mesothelin splice variants*
Fausther M, Lavoie E, Dranoff JA. Liver myofibroblasts of murine origins express mesothelin: Identification of novel rat mesothelin splice variants*. PLOS ONE 2017, 12: e0184499. PMID: 28898276, PMCID: PMC5595315, DOI: 10.1371/journal.pone.0184499.Peer-Reviewed Original ResearchConceptsHepatic stellate cellsLiver myofibroblastsStellate cellsFibrosis progressionLiver diseasePortal fibroblastsMesothelial cellsChronic cholestatic liver diseaseProgressive scar formationChronic liver diseaseCholestatic liver diseaseNormal mesothelial cellsSplice variantsEffector cellsOrgan failureCell surface moleculesHepatic fibrosisMyofibroblast proliferationMyofibroblast functionScar formationMesothelinPolyclonal ratCell markersMyofibroblastsCholangiocarcinoma cells
2015
Establishment and Characterization of Rat Portal Myofibroblast Cell Lines
Fausther M, Goree JR, Lavoie ÉG, Graham AL, Sévigny J, Dranoff JA. Establishment and Characterization of Rat Portal Myofibroblast Cell Lines. PLOS ONE 2015, 10: e0121161. PMID: 25822334, PMCID: PMC4378927, DOI: 10.1371/journal.pone.0121161.Peer-Reviewed Original ResearchConceptsHepatic stellate cellsPortal fibroblastsMyofibroblast cell lineLiver fibrosisCell linesAlpha 1Alpha-smooth muscle actinMyofibroblast marker alpha-smooth muscle actinScar-forming myofibroblastsSmooth muscle actinMesenchymal cell markersNTPDase2/CD39L1Lecithin retinol acyltransferaseStellate cellsCollagen alpha 1Cholangiocyte proliferationMetalloproteinases-1Muscle actinTissue inhibitorAdult rat liverCell markersCholangiocarcinoma cellsCulture activationRetinol acyltransferaseFunctional studies
2014
MCP‐1 downregulates MMP‐9 export via vesicular redistribution to lysosomes in rat portal fibroblasts
Hickman DA, Syal G, Fausther M, Lavoie EG, Goree JR, Storrie B, Dranoff JA. MCP‐1 downregulates MMP‐9 export via vesicular redistribution to lysosomes in rat portal fibroblasts. Physiological Reports 2014, 2: e12153. PMID: 25413315, PMCID: PMC4255798, DOI: 10.14814/phy2.12153.Peer-Reviewed Original Research
2012
Advances in cholangiocyte immunobiology
Syal G, Fausther M, Dranoff JA. Advances in cholangiocyte immunobiology. AJP Gastrointestinal And Liver Physiology 2012, 303: g1077-g1086. PMID: 22961800, PMCID: PMC3517647, DOI: 10.1152/ajpgi.00227.2012.Peer-Reviewed Original ResearchConceptsImmune responseMajor histocompatibility complex antigensExtrahepatic bile ductAdaptive immune responsesHistocompatibility complex antigensHepatic stellate cellsBiliary infectionBiliary cirrhosisInflammatory mediatorsBiliary tractPortal fibroblastsBile ductProfessional APCsBiliary systemInflammatory modulatorsImmune cellsComplex antigensStellate cellsDuct epitheliumMyofibroblastic differentiationIntracellular signaling cascadesCholangiocytesFirst lineAdhesion moleculesCytokinesActivated hepatic stellate cells upregulate transcription of ecto-5′-nucleotidase/CD73 via specific SP1 and SMAD promoter elements
Fausther M, Sheung N, Saiman Y, Bansal MB, Dranoff JA. Activated hepatic stellate cells upregulate transcription of ecto-5′-nucleotidase/CD73 via specific SP1 and SMAD promoter elements. AJP Gastrointestinal And Liver Physiology 2012, 303: g904-g914. PMID: 22899823, PMCID: PMC3469697, DOI: 10.1152/ajpgi.00015.2012.Peer-Reviewed Original ResearchConceptsHepatic stellate cellsPortal fibroblastsLiver myofibroblastsLiver fibrosisStellate cellsMyofibroblastic hepatic stellate cellsQuiescent hepatic stellate cellsActivated hepatic stellate cellsCD73 gene expressionCD73-deficient miceRegulation of CD73Experimental liver fibrosisPromising molecular targetCD73 geneLiver diseaseAdenosine generationNovel cellular markerAntifibrotic therapyExperimental fibrosisFibrous septaRate-limiting enzymeCD73 proteinMyofibroblastic differentiationFibrotic liverAdenosine production
2011
Coexpression of ecto-5′-nucleotidase/CD73 with specific NTPDases differentially regulates adenosine formation in the rat liver
Fausther M, Lecka J, Soliman E, Kauffenstein G, Pelletier J, Sheung N, Dranoff JA, Sévigny J. Coexpression of ecto-5′-nucleotidase/CD73 with specific NTPDases differentially regulates adenosine formation in the rat liver. AJP Gastrointestinal And Liver Physiology 2011, 302: g447-g459. PMID: 22135310, PMCID: PMC3287391, DOI: 10.1152/ajpgi.00165.2011.Peer-Reviewed Original ResearchConceptsRat liverRecombinant rat enzymeDistinct fibroblast populationsP2 receptor agonistsSmooth muscle cellsNTPDase2/CD39L1Vascular endothelial cellsFibrotic rat liverCD73 protein expressionSpecific biochemical propertiesPortal fibroblastsReceptor agonistP2 receptorsNormal rat liverFibrotic conditionsPortal spacesInhibitor ADPAdenosine formationMuscle cellsCD73Endothelial cellsTriphosphate diphosphohydrolaseFormation of adenosineProtein expressionEctonucleotidases
2009
Portal fibroblasts: Underappreciated mediators of biliary fibrosis
Dranoff JA, Wells RG. Portal fibroblasts: Underappreciated mediators of biliary fibrosis. Hepatology 2009, 51: 1438-1444. PMID: 20209607, PMCID: PMC2850946, DOI: 10.1002/hep.23405.Peer-Reviewed Original ResearchConceptsPortal fibroblastsNonparenchymal cell populationBiliary fibrosisStellate cellsCell populationsHepatic stellate cellsFibrogenic myofibroblastsChronic injuryBiliary epitheliumDuct epitheliumFibrotic liverUnderappreciated mediatorCollagen productionFurther studiesFibrosisLiverEpitheliumFibroblastsCellsFibrogenesisInjuryPopulationMyofibroblastsPathobiologyImportant role
2008
IL-6 downregulates transcription of NTPDase2 via specific promoter elements
Yu J, Lavoie E, Sheung N, Tremblay JJ, Sévigny J, Dranoff JA. IL-6 downregulates transcription of NTPDase2 via specific promoter elements. AJP Gastrointestinal And Liver Physiology 2008, 294: g748-g756. PMID: 18202114, PMCID: PMC5239663, DOI: 10.1152/ajpgi.00208.2007.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphatasesAnimalsBlotting, WesternCell DifferentiationCloning, MolecularCytokine Receptor gp130DNA, ComplementaryDown-RegulationElectrophoretic Mobility Shift AssayFibroblastsFluorescent Antibody TechniqueInterleukin-6LuciferasesMaleMicroscopy, ConfocalMutagenesis, Site-DirectedPromoter Regions, GeneticRatsRats, Sprague-DawleyResponse ElementsReverse Transcriptase Polymerase Chain ReactionConceptsBile ductular proliferationPortal fibroblastsIL-6Ductular proliferationBiliary cirrhosisIL-6 receptor gp80Alpha-smooth muscle actin expressionIL-6 responsePotential therapeutic approachMuscle actin expressionNTPDase2 expressionTime-dependent fashionBiliary fibrosisIL-6 receptor gp130Interleukin-6Therapeutic approachesResponse elementMyofibroblastic differentiationDiphosphohydrolase 2CirrhosisMRNA expressionActin expressionMinimal promoter constructProtein expressionIL-6 response element
2007
Transforming growth factor‐β and substrate stiffness regulate portal fibroblast activation in culture
Li Z, Dranoff JA, Chan EP, Uemura M, Sévigny J, Wells RG. Transforming growth factor‐β and substrate stiffness regulate portal fibroblast activation in culture. Hepatology 2007, 46: 1246-1256. PMID: 17625791, DOI: 10.1002/hep.21792.Peer-Reviewed Original ResearchConceptsHepatic stellate cellsPortal fibroblastsStellate cellsMyofibroblastic differentiationTGF-beta receptor kinase inhibitorGrowth factorAlpha-smooth muscle actinAlpha-smooth muscle actin expressionPlatelet-derived growth factorMuscle actin expressionReceptor kinase inhibitorBiliary fibrosisRat liver tissueFibroblast activationFibrogenic cellsMuscle actinLiver tissueMyofibroblastic phenotypeActin expressionFibroblast differentiationKinase inhibitorsDesminMyofibroblastsFibroblastsCells
2005
Secretion of MCP-1/CCL2 by bile duct epithelia induces myofibroblastic transdifferentiation of portal fibroblasts
Kruglov EA, Nathanson RA, Nguyen T, Dranoff JA. Secretion of MCP-1/CCL2 by bile duct epithelia induces myofibroblastic transdifferentiation of portal fibroblasts. AJP Gastrointestinal And Liver Physiology 2005, 290: g765-g771. PMID: 16282363, DOI: 10.1152/ajpgi.00308.2005.Peer-Reviewed Original ResearchConceptsBile duct epitheliumHepatic stellate cellsPortal fibroblastsMCP-1Biliary fibrosisDuct epitheliumMyofibroblastic transdifferentiationMCP-1/CCL2Fibrogenic liver cellsChemoattractant protein-1Ectonucleotidase NTPDase2PF proliferationAlpha-SMA levelsReceptor CCR2Stellate cellsParacrine fashionFunctional receptorsInduces proliferationImportant mediatorMuscle expressionFibrosisLiver cellsProtein 1Procollagen productionRecent evidencePortal Fibroblasts Regulate the Proliferation of Bile Duct Epithelia via Expression of NTPDase2*
Jhandier MN, Kruglov EA, Lavoie É, Sévigny J, Dranoff JA. Portal Fibroblasts Regulate the Proliferation of Bile Duct Epithelia via Expression of NTPDase2*. Journal Of Biological Chemistry 2005, 280: 22986-22992. PMID: 15799977, DOI: 10.1074/jbc.m412371200.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphatasesAnimalsBile DuctsBromodeoxyuridineCell ProliferationCholangiocarcinomaCholestasisCoculture TechniquesDNA, ComplementaryEpithelial CellsFibroblastsHumansLiverMaleMicroscopy, ConfocalMicroscopy, FluorescenceModels, BiologicalRatsRats, Sprague-DawleyReverse Transcriptase Polymerase Chain ReactionRNA, Small InterferingSignal TransductionTransfectionConceptsBile ductular proliferationExpression of NTPDase2Portal fibroblastsDuctular proliferationBile duct epitheliumNTPDase2 expressionMz-ChA-1 cellsPortal myofibroblastsP2Y receptorsDuct epitheliumBile duct-ligated ratsCell proliferationDuct-ligated ratsReal-time reverse transcription PCRQuantitative real-time reverse transcription PCRHuman cholangiocarcinoma cellsNovel co-culture modelMz-ChA-1 human cholangiocarcinoma cellsNucleotidase apyraseP2Y activationCo-culture modelObstructive cholestasisReverse transcription-PCRPathologic alterationsEpithelial proliferation
2004
Ectonucleotidase NTPDase2 Is Selectively Down-Regulated in Biliary Cirrhosis.
Dranoff J, Kruglov E, Toure J, Braun N, Zimmermann H, Jain D, Knowles A, Sévigny J. Ectonucleotidase NTPDase2 Is Selectively Down-Regulated in Biliary Cirrhosis. Journal Of Investigative Medicine 2004, 52: 475. DOI: 10.1097/00042871-200411000-00042.Peer-Reviewed Original ResearchBile duct ligationNTPDase2 expressionPrimary biliary cirrhosisBiliary cirrhosisPortal fibroblastsReal-time polymerase chain reactionCCl4 administrationPolymerase chain reactionBiopsy specimensPortal areasExperimental ratsFibrous bandsNormal liverConfocal immunofluorescenceExpression of NTPDase2Fibrogenic liver cellsHepatitis C. ConclusionsHepatitis C cirrhosisLiver biopsy specimensFibrotic liver diseaseChain reactionHuman liver biopsy specimensHepatic stellate cellsNew therapeutic approachesSmooth muscle actinEctonucleotidase NTPDase2 is Selectively Down-Regulated in Biliary Cirrhosis
Dranoff J, Kruglov E, Toure J, Braun N, Zimmermann H, Jain D, Knowles A, Sévigny J. Ectonucleotidase NTPDase2 is Selectively Down-Regulated in Biliary Cirrhosis. Journal Of Investigative Medicine 2004, 52: 475-482. DOI: 10.1177/108155890405200741.Peer-Reviewed Original ResearchBile duct ligationNTPDase2 expressionPrimary biliary cirrhosisBiliary cirrhosisPortal fibroblastsReal-time polymerase chain reactionPolymerase chain reactionBiopsy specimensPortal areasExperimental ratsFibrous bandsNormal liverConfocal immunofluorescenceExpression of NTPDase2Fibrogenic liver cellsHepatitis C cirrhosisLiver biopsy specimensFibrotic liver diseaseChain reactionHuman liver biopsy specimensHepatic stellate cellsNew therapeutic approachesSmooth muscle actinCarbon tetrachloride administrationTriphosphate diphosphohydrolase 2Ectonucleotidase NTPDase2 Is Selectively Down-Regulated in Biliary Cirrhosis
Dranoff JA, Kruglov EA, Toure J, Braun N, Zimmermann H, Jain D, Knowles AF, Sévigny J. Ectonucleotidase NTPDase2 Is Selectively Down-Regulated in Biliary Cirrhosis. Journal Of Investigative Medicine 2004, 52: 475. PMID: 15651265, DOI: 10.1136/jim-52-07-42.Peer-Reviewed Original ResearchConceptsBile duct ligationNTPDase2 expressionPrimary biliary cirrhosisBiliary cirrhosisPortal fibroblastsReal-time polymerase chain reactionCCl4 administrationPolymerase chain reactionBiopsy specimensPortal areasExperimental ratsFibrous bandsNormal liverConfocal immunofluorescenceAlpha-smooth muscle actinExpression of NTPDase2Fibrogenic liver cellsHepatitis C cirrhosisLiver biopsy specimensFibrotic liver diseaseHuman liver biopsy specimensChain reactionNew therapeutic approachesHepatic stellate cellsCarbon tetrachloride administrationAutocrine release of TGF‐β by portal fibroblasts regulates cell growth
Wells RG, Kruglov E, Dranoff JA. Autocrine release of TGF‐β by portal fibroblasts regulates cell growth. FEBS Letters 2004, 559: 107-110. PMID: 14960316, DOI: 10.1016/s0014-5793(04)00037-7.Peer-Reviewed Original ResearchConceptsHepatic stellate cellsPortal fibroblastsBiliary fibrosisGrowth factorTGF-beta2Activated hepatic stellate cellsDerived growth factorTGF-beta receptorsFibroblast growth factorPF proliferationMyofibroblast populationStellate cellsFibrogenic cellsKey growth factorsAutocrine releaseFibrosisCell growthFibroblastsCellsPopulationFactorsTGFLiverReceptors
2002
The ecto‐nucleoside triphosphate diphosphohydrolase NTPDase2/CD39L1 is expressed in a novel functional compartment within the liver
Dranoff JA, Kruglov EA, Robson SC, Braun N, Zimmermann H, Sévigny J. The ecto‐nucleoside triphosphate diphosphohydrolase NTPDase2/CD39L1 is expressed in a novel functional compartment within the liver. Hepatology 2002, 36: 1135-1144. PMID: 12395323, DOI: 10.1053/jhep.2002.36823.Peer-Reviewed Original ResearchConceptsIntrahepatic bile ductsExtracellular nucleotidesBile ductDiverse biological functionsBlot analysisEcto-nucleoside triphosphate diphosphohydrolasesNTPDase2/CD39L1Portal fibroblastsNorthern blot analysisCellular compartmentsBiological functionsPotential regulatorConfocal immunofluorescenceWestern blot analysisHepatic blood flowBile duct epitheliumReverse transcription-polymerase chain reactionFunctional assaysTriphosphate diphosphohydrolasesImmunoelectron microscopyFunctional compartmentsHepatic central veinNucleotidesNTPDase1NTPDase2