2022
Review of existing evidence demonstrates that methotrexate does not cause liver fibrosis
Cheema HI, Haselow D, Dranoff JA. Review of existing evidence demonstrates that methotrexate does not cause liver fibrosis. Journal Of Investigative Medicine 2022, 70: 1452-1460. PMID: 36002175, DOI: 10.1136/jim-2021-002206.Peer-Reviewed Original ResearchConceptsChronic liver diseaseLiver diseaseLiver fibrosisLiver injuryPre-existing chronic liver diseaseNon-alcoholic fatty liver diseaseLong-term methotrexateMeta-analysis portionProgressive liver injurySerial liver biopsiesFatty liver diseaseAdvanced liver fibrosisCare of patientsMetabolic liver diseaseNon-invasive assessmentComprehensive literature searchAssessment of injuryMethotrexate doseAdvanced fibrosisCommon indicationDirect causeLiver biopsyTherapeutic dosesRisk factorsInclusion criteria
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
Coffee 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 acts
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
I drink for my liver, Doc: emerging evidence that coffee prevents cirrhosis
Feld JJ, Lavoie ÉG, Fausther M, Dranoff JA. I drink for my liver, Doc: emerging evidence that coffee prevents cirrhosis. F1000Research 2015, 4: 95. PMID: 25977756, PMCID: PMC4416533, DOI: 10.12688/f1000research.6368.2.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsChronic liver diseaseSalutary effectsLiver diseaseLiver fibrosisHepatocellular carcinomaNovel pharmacologic treatmentsCoffee ingestionPharmacologic treatmentFibrosis pathogenesisObservational studyRegular ingestionCoffee consumptionEpidemiological dataPharmacological effectsCaffeine consumptionCirrhosisDecaffeinated coffeeCaffeine effectsEffector moleculesPatientsFibrosisPathogenesisDiseaseIngestionConsistent effectStrategies and endpoints of antifibrotic drug trials: Summary and recommendations from the AASLD Emerging Trends Conference, Chicago, June 2014
Torok NJ, Dranoff JA, Schuppan D, Friedman SL. Strategies and endpoints of antifibrotic drug trials: Summary and recommendations from the AASLD Emerging Trends Conference, Chicago, June 2014. Hepatology 2015, 62: 627-634. PMID: 25626988, PMCID: PMC4515973, DOI: 10.1002/hep.27720.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsClinical trial designTrial designLiver diseaseLiver fibrosisClinical trialsFuture clinical trial designChronic liver diseaseOff-target toxicityKey unmetPotential off-target toxicityAntifibrotic agentsNoninvasive markerAntifibrotic therapyAntifibrotic drugsPreclinical proofDrug trialsStudy groupRisk populationsPharmacological targetsTrialsExpert overviewFibrosisDiseaseEndpointAmerican AssociationI drink for my liver, Doc: emerging evidence that coffee prevents cirrhosis
Feld J, Lavoie É, Fausther M, Dranoff J. I drink for my liver, Doc: emerging evidence that coffee prevents cirrhosis. F1000Research 2015, 4: 95. DOI: 10.12688/f1000research.6368.1.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsChronic liver diseaseSalutary effectsLiver diseaseLiver fibrosisHepatocellular carcinomaNovel pharmacologic treatmentsCoffee ingestionPharmacologic treatmentFibrosis pathogenesisObservational studyRegular ingestionCoffee consumptionEpidemiological dataPharmacological effectsCaffeine consumptionCirrhosisDecaffeinated coffeeCaffeine effectsEffector moleculesPatientsFibrosisPathogenesisDiseaseIngestionConsistent effectEstablishment 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 ResearchHow does coffee prevent liver fibrosis? biological plausibility for recent epidemiological observations
Dranoff JA, Feld JJ, Lavoie É, Fausther M. How does coffee prevent liver fibrosis? biological plausibility for recent epidemiological observations. Hepatology 2014, 60: 464-467. PMID: 24464631, PMCID: PMC4110162, DOI: 10.1002/hep.27032.Peer-Reviewed Original Research
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 regulationFibrinolysisExocytosisMyofibroblastsReleaseContribution of Myofibroblasts of Different Origins to Liver Fibrosis
Fausther M, Lavoie EG, Dranoff JA. Contribution of Myofibroblasts of Different Origins to Liver Fibrosis. Current Pathobiology Reports 2013, 1: 225-230. PMID: 23997993, PMCID: PMC3755779, DOI: 10.1007/s40139-013-0020-0.Peer-Reviewed Original ResearchHepatic fibrosisLiver fibrosisLiver myofibroblastsContribution of myofibroblastsProgressive liver fibrosisPrimary effector cellsTissue repair responseExtracellular matrix accumulationMajor fibrogenic cellsLiver failureLiver injuryEffector cellsCurrent therapiesAntifibrotic therapyCommon causeScar formationFibrogenic cellsFibrosisMatrix accumulationExtracellular matrix synthesisMyofibroblastsPromising targetWound healingRepair responseTherapyCXCL12 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
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 expression
2009
Intracellular 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
Molecular 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