2019
Reduction in SNAP-23 Alters Microfilament Organization in Myofibrobastic Hepatic Stellate Cells.
Eubanks HB, Lavoie EG, Goree J, Kamykowski JA, Gokden N, Fausther M, Dranoff JA. Reduction in SNAP-23 Alters Microfilament Organization in Myofibrobastic Hepatic Stellate Cells. Gene Expression 2019, 20: 25-37. PMID: 31757226, PMCID: PMC7284106, DOI: 10.3727/105221619x15742818049365.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonActin Depolymerizing FactorsActinsAnimalsCarbon TetrachlorideCell LineCell MovementCell SeparationGene Knockdown TechniquesHepatic Stellate CellsHumansLiverLiver CirrhosisMiceMyofibroblastsQb-SNARE ProteinsQc-SNARE ProteinsRho-Associated KinasesRNA InterferenceRNA, Small InterferingSignal TransductionStress FibersWound HealingConceptsSNAP-23T-SNARE proteinsSpecific SNARE proteinsMyofibroblastic hepatic stellate cellsSNARE proteinsActin cytoskeletonActin dynamicsHepatic stellate cellsCytoskeletal reorganizationCell movementPlasma membraneHomologous proteinsExtracellular environmentMicrofilament organizationSNAP-25HSC phenotypeReceptor proteinProteinStellate cellsQuiescent hepatic stellate cellsPhenotypeCellsCritical effector cellsCytoskeletonVivo
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
2016
Sortilin Deficiency Reduces Ductular Reaction, Hepatocyte Apoptosis, and Liver Fibrosis in Cholestatic-Induced Liver Injury
Hubel E, Saroha A, Park WJ, Pewzner-Jung Y, Lavoie EG, Futerman AH, Bruck R, Fishman S, Dranoff JA, Shibolet O, Zvibel I. Sortilin Deficiency Reduces Ductular Reaction, Hepatocyte Apoptosis, and Liver Fibrosis in Cholestatic-Induced Liver Injury. American Journal Of Pathology 2016, 187: 122-133. PMID: 27842214, DOI: 10.1016/j.ajpath.2016.09.005.Peer-Reviewed Original ResearchConceptsBile duct ligationSerum IL-6IL-6Hepatocyte apoptosisWT miceLiver fibrosisCholangiocyte proliferationHepatic stellate cell activationCholestatic liver damageIL-6 neutralizationStellate cell activationHepatic stellate cellsASMase activityCarbon tetrachloride treatmentCarbon tetrachloride modelSortilin deficiencyHepatic inflammationLiver inflammationHepatocellular injuryLiver injuryLiver damageHepatic fibrosisBiliary damageDuctular reactionDuct ligation
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
2013
Posttranslational regulation of tissue inhibitor of metalloproteinase‐1 by calcium‐dependent vesicular exocytosis
Dranoff JA, Bhatia N, Fausther M, Lavoie EG, Granell S, Baldini G, Hickman DA, Sheung N. Posttranslational regulation of tissue inhibitor of metalloproteinase‐1 by calcium‐dependent vesicular exocytosis. Physiological Reports 2013, 1: e00125. PMID: 24400134, PMCID: PMC3871447, DOI: 10.1002/phy2.125.Peer-Reviewed Original ResearchHepatic stellate cellsMyofibroblastic hepatic stellate cellsLiver fibrosisMetalloproteinase-1Tissue inhibitorVesicular exocytosisTIMP-1 releaseLiver myofibroblastsStellate cellsTIMP-1FibrosisCritical mediatorNew targetsInhibitorsPosttranslational regulationFibrinolysisExocytosisMyofibroblastsReleaseCXCL12 induces hepatic stellate cell contraction through a calcium-independent pathway
Saiman Y, Agarwal R, Hickman DA, Fausther M, El-Shamy A, Dranoff JA, Friedman SL, Bansal MB. CXCL12 induces hepatic stellate cell contraction through a calcium-independent pathway. AJP Gastrointestinal And Liver Physiology 2013, 305: g375-g382. PMID: 23812037, PMCID: PMC3761245, DOI: 10.1152/ajpgi.00185.2012.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsCalciumCell LineCell ShapeChelating AgentsChemokine CXCL12CollagenDose-Response Relationship, DrugGelsHepatic Stellate CellsHumansMiceMyosin Light ChainsPhenotypePhosphorylationProtein Kinase InhibitorsReceptors, CXCR4Recombinant ProteinsRho-Associated KinasesRNA InterferenceSignal TransductionTransfectionConceptsHepatic stellate cellsChronic liver diseaseStellate cell contractionPortal hypertensionLiver diseaseLiver fibrosisSmall molecule inhibitorsStimulation of HSCsHepatic stellate cell contractionEnd-stage liver diseaseGel contractionActivated hepatic stellate cellsAddition of AMD3100Functional chemokine receptorsIntrahepatic blood flowCXCR4-dependent mannerCell contractionDeath of patientsRho-kinase pathwayMolecule inhibitorsCollagen gel latticeRho-kinase inhibitorCalcium-independent fashionCalcium-independent pathwayMyosin light chain phosphorylation
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
New insights on the pathogenesis of biliary cirrhosis provided by studies in FXR knockout mice
Fausther M, Dranoff JA. New insights on the pathogenesis of biliary cirrhosis provided by studies in FXR knockout mice. Journal Of Hepatology 2011, 55: 939-940. PMID: 21672564, PMCID: PMC3756144, DOI: 10.1016/j.jhep.2011.04.013.Peer-Reviewed Original ResearchHepatic stellate cellsHuman hepatic stellate cellsFarnesoid X receptorLiver fibrosisBiliary typeMouse modelCommon bile duct ligationNuclear bile acid receptorFXR protein expressionMouse hepatic stellate cellsFibrotic liver diseaseBile acid receptorBile duct ligationDifferent mouse modelsFXR knockout miceVitamin D receptorReceptor expression levelsDirect therapeutic targetsBiliary cirrhosisLiver diseaseHepatic fibrosisDuct ligationFXR expressionD receptorLiver expressionActivated Hepatic Stellate Cells Transcriptionally Upregulate Ecto-5'-Nucleotidase/CD73 via Specific Promoter Elements
Fausther M, Dranoff J. Activated Hepatic Stellate Cells Transcriptionally Upregulate Ecto-5'-Nucleotidase/CD73 via Specific Promoter Elements. Gastroenterology 2011, 140: s-915-s-916. DOI: 10.1016/s0016-5085(11)63798-0.Peer-Reviewed Original Research
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 roleIntracellular calcium signals regulate growth of hepatic stellate cells via specific effects on cell cycle progression
Soliman EM, Rodrigues MA, Gomes DA, Sheung N, Yu J, Amaya MJ, Nathanson MH, Dranoff JA. Intracellular calcium signals regulate growth of hepatic stellate cells via specific effects on cell cycle progression. Cell Calcium 2009, 45: 284-292. PMID: 19131107, PMCID: PMC3018528, DOI: 10.1016/j.ceca.2008.11.006.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalcium SignalingCalcium-Calmodulin-Dependent Protein Kinase Type 2Cdc25 PhosphatasesCell CompartmentationCell CycleCell NucleusCell ProliferationChelating AgentsCytosolEgtazic AcidEnzyme InhibitorsG2 PhaseHepatocytesHumansIntracellular SpaceParvalbuminsPhosphorylationProtein TransportRatsSubcellular FractionsConceptsHepatic stellate cellsLiver fibrosisStellate cellsImmortalized human hepatic stellate cellsHSC growthHuman hepatic stellate cellsRat hepatic stellate cellsPrimary rat hepatic stellate cellsIntracellular calcium signalsCdc25C phosphorylationPharmacological therapyCalmodulin kinase IIImportant mediatorCell cycle progressionHSC proliferationCell proliferationLogical targetCalcium signalsAdenoviral constructDownstream intracellularG2/M checkpointCaMK IIFibrosisBlockadeParvalbumin
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 inhibitorsDesminMyofibroblastsFibroblastsCellsSuccinate is a paracrine signal for liver damage
Correa PR, Kruglov EA, Thompson M, Leite MF, Dranoff JA, Nathanson MH. Succinate is a paracrine signal for liver damage. Journal Of Hepatology 2007, 47: 262-269. PMID: 17451837, PMCID: PMC1986575, DOI: 10.1016/j.jhep.2007.03.016.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsFluorescent Antibody TechniqueIn Vitro TechniquesInfusions, IntravenousIschemiaLiverLiver DiseasesMaleParacrine CommunicationPerfusionPortal VeinPressureRatsRats, Sprague-DawleyReceptors, G-Protein-CoupledReverse Transcriptase Polymerase Chain ReactionSignal TransductionSuccinic AcidTissue DistributionConceptsHepatic stellate cellsSuccinate receptorParacrine signalsStellate cell activationStellate cellsCell expression systemTime-lapse imagingRelease of succinateCell activationCytosolic Ca2Effect of succinatePrimary hepatic stellate cellsHepatic cell typesExpression systemQuiescent hepatic stellate cellsConfocal immunofluorescencePhysiological roleIschemic hepatocytesCell typesBiochemical assaysSingle cellsLiver damageBACKGROUND/Western blotCAMP productionMolecular basis for calcium signaling in hepatic stellate cells
Kruglov EA, Correa PR, Arora G, Yu J, Nathanson MH, Dranoff JA. Molecular basis for calcium signaling in hepatic stellate cells. AJP Gastrointestinal And Liver Physiology 2007, 292: g975-g982. PMID: 17204544, DOI: 10.1152/ajpgi.00401.2006.Peer-Reviewed Original ResearchMeSH KeywordsActive Transport, Cell NucleusAdenosine TriphosphateAnimalsCalcium SignalingCalreticulinCell NucleusCell ShapeCell Surface ExtensionsCells, CulturedEndoplasmic ReticulumInositol 1,4,5-Trisphosphate ReceptorsLiverLiver CirrhosisMaleMicroscopy, ConfocalMicroscopy, VideoRatsRats, Sprague-DawleyReceptors, Purinergic P2RNA, MessengerTime FactorsConceptsHepatic stellate cellsCell extensionsLipid-storing cellsSubcellular organizationLiver fibrosisMolecular basisStellate cellsSubcellular signalingTrisphosphate receptorChronic liver failureProgressive liver fibrosisSufficient machineryExtracellular ATPMyofibroblastic transdifferentiationOrgan fibrosisLiver failureP2Y receptorsHealthy liverATPLocal controlCellsCritical stepLocal applicationImportant mediatorFibrosisPrevention of liver fibrosis by the purinoceptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulfonate (PPADS).
Dranoff JA, Kruglov EA, Abreu-Lanfranco O, Nguyen T, Arora G, Jain D. Prevention of liver fibrosis by the purinoceptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulfonate (PPADS). In Vivo 2007, 21: 957-65. PMID: 18210741.Peer-Reviewed Original ResearchConceptsHepatic stellate cellsBile duct ligationLiver fibrosisDuct ligationPurinergic receptorsCommon bile duct ligationEffect of PPADSPurinergic receptor inhibitorsDevelopment of cirrhosisHSC proliferationEffective pharmacologic treatmentExperimental liver fibrosisAnnexin V flow cytometryEffect of suraminSirius red stainQuantitative RT-PCRPharmacologic treatmentReceptor inhibitorsPPADSStellate cellsLiver sectionsFibrosisBromodeoxyuridine uptakePurinoceptor activationExperimental animals
2006
Adenosine inhibits cytosolic calcium signals and chemotaxis in hepatic stellate cells
Hashmi AZ, Hakim W, Kruglov EA, Watanabe A, Watkins W, Dranoff JA, Mehal WZ. Adenosine inhibits cytosolic calcium signals and chemotaxis in hepatic stellate cells. AJP Gastrointestinal And Liver Physiology 2006, 292: g395-g401. PMID: 17053161, PMCID: PMC3224076, DOI: 10.1152/ajpgi.00208.2006.Peer-Reviewed Original ResearchConceptsCytosolic Ca2Collagen I mRNATGF-beta productionHepatic stellate cell biologyLX-2 cellsEffects of adenosineHepatic stellate cellsSite of injuryI mRNAElevated tissue levelsDose-dependent mannerHigh adenosine concentrationsStellate cell biologyAdenylate cyclase inhibitorActivation markersLiver fibrosisTissue injuryHSC chemotaxisStellate cellsCyclase inhibitorAdenosine concentrationTranswell systemInhibited increasesCellular hypoxiaTissue levels
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 evidence
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 actin