2023
Effects of short‐term supervised exercise training on liver fat in adolescents with obesity: a randomized controlled trial
Tas E, Landes R, Diaz E, Bai S, Ou X, Buchmann R, Na X, Muzumdar R, Børsheim E, Dranoff J. Effects of short‐term supervised exercise training on liver fat in adolescents with obesity: a randomized controlled trial. Obesity 2023, 31: 2740-2749. PMID: 37731271, PMCID: PMC11519784, DOI: 10.1002/oby.23887.Peer-Reviewed Original ResearchConceptsHigh-intensity interval trainingCardiorespiratory fitnessOral glucose tolerance testDual-energy X-ray absorptiometryAttenuation parameter (CAP) scoreIntrahepatic triglyceride contentSerum alanine aminotransferaseGlucose tolerance testSteatotic liver diseaseX-ray absorptiometryLiver magnetic resonanceCardiometabolic markersCardiometabolic healthExercise trainingHIIT protocolsLiver diseaseLiver fatExercise protocolTolerance testCRF testAlanine aminotransferaseInterval trainingMRI-PDFFTriglyceride contentObesity
2022
Obesity, but not glycemic control, predicts liver steatosis in children with type 1 diabetes
Tas E, Bai S, Mak D, Diaz E, Dranoff J. Obesity, but not glycemic control, predicts liver steatosis in children with type 1 diabetes. Journal Of Diabetes And Its Complications 2022, 36: 108341. PMID: 36345110, DOI: 10.1016/j.jdiacomp.2022.108341.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseBody mass indexMajor risk factorType 1 diabetesHDL ratioHDL cholesterolLiver diseaseClinical parametersRisk factorsCAP scoresDiagnostic performanceReceiver operator curve analysisCommon liver diseaseFatty liver diseaseNon-diabetic childrenNon-obese subjectsFindings of childrenCross-sectional studyNAFLD statusClinical characteristicsGlycemic controlObese groupObese subjectsFurther workupMass indexReview 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
2020
Fibroblast Growth Factor-21 to Adiponectin Ratio: A Potential Biomarker to Monitor Liver Fat in Children With Obesity
Tas E, Bai S, Ou X, Mercer K, Lin H, Mansfield K, Buchmann R, Diaz EC, Oden J, Børsheim E, Adams SH, Dranoff J. Fibroblast Growth Factor-21 to Adiponectin Ratio: A Potential Biomarker to Monitor Liver Fat in Children With Obesity. Frontiers In Endocrinology 2020, 11: 654. PMID: 33071964, PMCID: PMC7533567, DOI: 10.3389/fendo.2020.00654.Peer-Reviewed Original ResearchConceptsNon-alcoholic fatty liver diseaseMagnetic resonance imagingIntrahepatic triglyceridesPercent changePotential biomarkersClinical weight loss programSerum fibroblast growth factorFibroblast growth factor 21Liver fat percentFatty liver diseaseWeight loss programGrowth factor 21Non-invasive biomarkersFibroblast growth factorCourse diseaseSerum FGF21Adiponectin ratioFinal visitAdiponectin levelsLiver biopsyLiver diseaseObese childrenLoss programLiver fatFactor 21
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 cellsCoffee 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 Statements
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
Expression of mediators of purinergic signaling in human liver cell lines
Goree JR, Lavoie EG, Fausther M, Dranoff JA. Expression of mediators of purinergic signaling in human liver cell lines. Purinergic Signalling 2014, 10: 631-638. PMID: 25194703, PMCID: PMC4272373, DOI: 10.1007/s11302-014-9425-4.Peer-Reviewed Original ResearchConceptsLiver cell subpopulationsPurinergic signalingPurinergic signalsCell subpopulationsCell linesExpression of mediatorsLiver disease pathogenesisHuman liver cell lineHuman cell line modelsCell line modelsLiver cell lineHepatic functionP2Y receptorsP2X receptorsLX-2Disease pathogenesisAdenosine receptorsLiver physiologyRT-PCRReceptorsHuman cell linesPurinergicLiverSubpopulationsSignalingPathological 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
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
2007
Succinate 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 mediatorFibrosis
2006
Cloning, purification, and identification of the liver canalicular ecto-ATPase as NTPDase8
Fausther M, Lecka J, Kukulski F, Lévesque S, Pelletier J, Zimmermann H, Dranoff JA, Sévigny J. Cloning, purification, and identification of the liver canalicular ecto-ATPase as NTPDase8. AJP Gastrointestinal And Liver Physiology 2006, 292: g785-g795. PMID: 17095758, PMCID: PMC3952495, DOI: 10.1152/ajpgi.00293.2006.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphatasesAmino Acid SequenceAnimalsAntigens, CDApyraseCatalysisCell LineChlorocebus aethiopsCloning, MolecularCOS CellsDeoxycholic AcidEnzyme InhibitorsHepatocytesHumansKineticsLiverMolecular Sequence DataNucleotidesRatsRats, Sprague-DawleyRecombinant ProteinsSequence Homology, Amino AcidSodium AzideSubstrate SpecificityConceptsExtracellular nucleotidesSpecific transmembrane receptorsAmino acid sequenceTerminal amino acid sequenceHEK293T cellsCritical liver functionsNTPDase2/CD39L1Cell surface enzymeTransmembrane receptorsAcid sequenceHigh identityCOS-7Recombinant proteinsNTPDase8Molecular identityNucleoside salvageEcto-ATPaseAffigel BlueNTPDase3 expressionAdenosine 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