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
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
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 regulationFibrinolysisExocytosisMyofibroblastsRelease
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
Activated 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
Expression of P2Y nucleotide receptors and ectonucleotidases in quiescent and activated rat hepatic stellate cells
Dranoff JA, Ogawa M, Kruglov EA, Gaça M, Sévigny J, Robson SC, Wells RG. Expression of P2Y nucleotide receptors and ectonucleotidases in quiescent and activated rat hepatic stellate cells. AJP Gastrointestinal And Liver Physiology 2004, 287: g417-g424. PMID: 14764443, PMCID: PMC5241161, DOI: 10.1152/ajpgi.00294.2003.Peer-Reviewed Original ResearchConceptsHepatic stellate cellsActivated hepatic stellate cellsQuiescent hepatic stellate cellsP2Y receptorsExtracellular nucleotidesP2Y subtypesStellate cellsMRNA expressionRT-PCRInhibitor suraminP2Y receptor subtypesReceptor subtype expressionExpression of mediatorsExpression of receptorsFunctional P2Y receptorsRat hepatic stellate cellsReal-time RT-PCRP2Y nucleotide receptorsEctonucleotidase expressionLiver fibrosisReceptor subtypesSubtype expressionEctonucleotidase activityExtracellular UDPFibrogenic cellsAutocrine 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
Isolation of Primary Rat Liver Fibroblasts
Kruglov EA, Jain D, Dranoff JA. Isolation of Primary Rat Liver Fibroblasts. Journal Of Investigative Medicine 2002, 50: 179. PMID: 12033282, DOI: 10.2310/6650.2002.33431.Peer-Reviewed Original ResearchConceptsLiver fibroblastsProcollagen-1 mRNAReverse transcription-polymerase chain reactionRat liverTranscription-polymerase chain reactionDistinct liver cell populationsSmooth muscle actinSmooth muscle cellsStandard cell culture methodsLiver cell populationsRole of fibroblastsVon Willebrand factorPolymerase chain reactionStellate cellsProcollagen 1Muscle actinCell markersMuscle cellsLiver physiologyAppearance of cellsWillebrand factorFibroblast morphologyChain reactionLiver researchCell populations