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 cellsThe Cholangiocyte Adenosine‐IL-6 Axis Regulates Survival During Biliary Cirrhosis
Lavoie EG, Fausther M, Goree JR, Dranoff JA. The Cholangiocyte Adenosine‐IL-6 Axis Regulates Survival During Biliary Cirrhosis. Gene Expression 2017, 17: 327-340. PMID: 28893353, PMCID: PMC5885153, DOI: 10.3727/105221617x15042723767876.Peer-Reviewed Original ResearchConceptsBile duct ligationIL-6 releaseExogenous IL-6Common bile duct ligationBiliary cirrhosisIL-6Duct ligationInjury responseIL-6 mRNA expressionIL-6 upregulationIL-6 secretionA2B adenosine receptorsLiver cell typesA2BAR activationBile infarctsInflammatory cellsCirrhosisEpithelial responseH69 cellsIntracellular Ca2Adenosine receptorsExtracellular adenosineInduces releaseMRNA expressionRegulates SurvivalCoffee Consumption and Prevention of Cirrhosis: In Support of the Caffeine Hypothesis
Dranoff JA. Coffee Consumption and Prevention of Cirrhosis: In Support of the Caffeine Hypothesis. Gene Expression 2017, 18: 1-3. PMID: 28893365, PMCID: PMC5885142, DOI: 10.3727/105221617x15046391179559.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsAn Elf2-like transcription factor acts as repressor of the mouse ecto-5′-nucleotidase gene expression in hepatic myofibroblasts
Fausther M, Lavoie EG, Goree JR, Dranoff JA. An Elf2-like transcription factor acts as repressor of the mouse ecto-5′-nucleotidase gene expression in hepatic myofibroblasts. Purinergic Signalling 2017, 13: 417-428. PMID: 28667437, PMCID: PMC5714833, DOI: 10.1007/s11302-017-9570-7.Peer-Reviewed Original ResearchConceptsLiver myofibroblastsHepatic fibrosisChronic liver injuryNon-parenchymal liver cellsTissue repair processEffector cellsLiver injuryLiver fibrosisHepatic myofibroblastsMyofibroblast functionContractile propertiesPathological wound healingExtracellular adenosineMyofibroblastsImportant mediatorPromoter transcriptional activityFibrosisLiver cellsGene expressionWound healingEndogenous moleculesImportant regulatorHeterogeneous populationLocal microenvironmentFactor actsTransforming Growth Factors α and β Are Essential for Modeling Cholangiocarcinoma Desmoplasia and Progression in a Three-Dimensional Organotypic Culture Model
Manzanares MÁ, Usui A, Campbell DJ, Dumur CI, Maldonado GT, Fausther M, Dranoff JA, Sirica AE. Transforming Growth Factors α and β Are Essential for Modeling Cholangiocarcinoma Desmoplasia and Progression in a Three-Dimensional Organotypic Culture Model. American Journal Of Pathology 2017, 187: 1068-1092. PMID: 28315313, PMCID: PMC5417049, DOI: 10.1016/j.ajpath.2017.01.013.Peer-Reviewed Original ResearchConceptsIntrahepatic cholangiocarcinomaOrganotypic culture modelDesmoplastic reactionThree-dimensional organotypic culture modelsCulture modelMesenchymal cell originCholangiocarcinoma cell growthCancer-associated myofibroblastsGrowth factor αAggressive malignancyDense fibrocollagenous stromaMalignant gradingCell anaplasiaSitu tumorsExtracellular vesicles carry microRNA‐195 to intrahepatic cholangiocarcinoma and improve survival in a rat model
Li L, Piontek K, Ishida M, Fausther M, Dranoff JA, Fu R, Mezey E, Gould SJ, Fordjour FK, Meltzer SJ, Sirica AE, Selaru FM. Extracellular vesicles carry microRNA‐195 to intrahepatic cholangiocarcinoma and improve survival in a rat model. Hepatology 2017, 65: 501-514. PMID: 27474881, PMCID: PMC5258762, DOI: 10.1002/hep.28735.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBile Duct NeoplasmsCarcinogenesisCell MovementCholangiocarcinomaDisease Models, AnimalDown-RegulationExtracellular VesiclesFibroblastsHumansImmunohistochemistryMaleMicroRNAsRandom AllocationRatsRats, Inbred F344Real-Time Polymerase Chain ReactionSensitivity and SpecificitySurvival RateTransfectionTumor Cells, CulturedTumor MicroenvironmentConceptsExtracellular vesiclesMiR speciesCancer cellsCancer-associated fibroblastsFibroblasts-derived extracellular vesiclesMiR-195Rat modelMicroRNA speciesQuantitative reverse transcription polymerase chain reactionCCA cellsSpeciesCancer developmentCancer fibroblastsHuman cholangiocarcinomaMiR contentReverse transcription-polymerase chain reactionNovel therapeuticsFibroblastsCentral roleSize of cancerVesiclesCellsPolymerase chain reactionMicroRNA-195Cancer microenvironment
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 studiesBeyond scar formation: Portal myofibroblast‐mediated angiogenesis in the fibrotic liver
Fausther M, Dranoff JA. Beyond scar formation: Portal myofibroblast‐mediated angiogenesis in the fibrotic liver. Hepatology 2015, 61: 766-768. PMID: 25502320, PMCID: PMC5115210, DOI: 10.1002/hep.27653.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
2014
Macrophage Heterogeneity in Liver Injury: You Are Now Leaving Kupffertown
Dranoff JA. Macrophage Heterogeneity in Liver Injury: You Are Now Leaving Kupffertown. Gastroenterology 2014, 147: 1430-1431. PMID: 25457848, DOI: 10.1053/j.gastro.2014.10.020.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsNT5E Mutations That Cause Human Disease Are Associated with Intracellular Mistrafficking of NT5E Protein
Fausther M, Lavoie EG, Goree JR, Baldini G, Dranoff JA. NT5E Mutations That Cause Human Disease Are Associated with Intracellular Mistrafficking of NT5E Protein. PLOS ONE 2014, 9: e98568. PMID: 24887587, PMCID: PMC4041762, DOI: 10.1371/journal.pone.0098568.Peer-Reviewed Original ResearchConceptsHuman diseasesWild typeCOS-7 kidney cellsWild-type proteinNovel genetic causesSubcellular traffickingER retentionMalachite green assayHeterologous expressionType proteinDefective proteinMutant fusionTrafficking defectsPlasma membraneExtracellular environmentGene mutationsDegradation of AMPBiochemical activityConfocal immunofluorescenceDistinct familiesWestern blot analysisCatalytic functionSynthetic apparatusMutant humanCell surfaceIntegrins, myofibroblasts, and organ fibrosis
Fausther M, Dranoff JA. Integrins, myofibroblasts, and organ fibrosis. Hepatology 2014, 60: 756-758. PMID: 24700390, PMCID: PMC4110176, DOI: 10.1002/hep.27155.Peer-Reviewed Original ResearchPathological Changes in Pulmonary Circulation in Carbon Tetrachloride (ccl4)-Induced Cirrhotic Mice
Das M, Boerma M, Goree JR, Lavoie EG, Fausther M, Gubrij IB, Pangle AK, Johnson LG, Dranoff JA. Pathological Changes in Pulmonary Circulation in Carbon Tetrachloride (ccl4)-Induced Cirrhotic Mice. PLOS ONE 2014, 9: e96043. PMID: 24763616, PMCID: PMC3999097, DOI: 10.1371/journal.pone.0096043.Peer-Reviewed Original ResearchConceptsPulmonary acceleration timeCirrhotic micePortopulmonary hypertensionPulmonary circulationPathological changesSpleen weight/body weight ratioVentricle weight/body weightWeight/body weight ratioChronic CCl4 treatmentPulmonary vascular diseaseMale C57BL/6 miceBody weight ratioTimes/weekOxidative stress markersNovel therapeutic interventionsPicrosirius red stainingSterile olive oilPortal hypertensionEffects of CCl4Pulmonary arteryC57BL/6 micePathophysiological mechanismsPulmonary vasculaturePerivascular collagenVascular disease
2013
CXCL12 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
Activated 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 roleTranscriptional regulation of IL-6 in bile duct epithelia by extracellular ATP
Yu J, Sheung N, Soliman EM, Spirli C, Dranoff JA. Transcriptional regulation of IL-6 in bile duct epithelia by extracellular ATP. AJP Gastrointestinal And Liver Physiology 2009, 296: g563-g571. PMID: 19136380, PMCID: PMC2660176, DOI: 10.1152/ajpgi.90502.2008.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsAntibodiesBile DuctsCalciumCalcium SignalingCell Line, TransformedCell Line, TumorCyclic AMPEpithelial CellsExtracellular SpaceFibroblastsHumansImmunoblottingInterleukin-6MaleMutagenesis, Site-DirectedPromoter Regions, GeneticRatsRats, Sprague-DawleyReceptors, Purinergic P2Response ElementsRNA, MessengerSignal TransductionTranscriptional ActivationConceptsBile duct epitheliumIL-6IL-6 transcriptionDuct epitheliumLiver injuryCAMP response elementP2Y11 receptorInflammatory cytokines IL-6Extracellular ATPIL-6 upregulationUse of agonistsRat bile duct epitheliaCytokines IL-6IL-6 releaseIL-6 promoter activityIL-6 mRNAExtracellular ATP actsCalcium agonistP2Y receptorsPharmacological profileHepatic responseCalcium-dependent fashionExtracellular nucleotidesCytosolic calciumPurinergic signals