2022
Short‐Term Safety of Repeated Acetaminophen Use in Patients With Compensated Cirrhosis
McGill MR, James LP, McCullough SS, Moran JH, Mathews SE, Peterson EC, Fleming DP, Tripod ME, Vazquez JH, Kennon‐McGill S, Spencer HJ, Dranoff JA. Short‐Term Safety of Repeated Acetaminophen Use in Patients With Compensated Cirrhosis. Hepatology Communications 2022, 6: 361-373. PMID: 34558847, PMCID: PMC8793989, DOI: 10.1002/hep4.1810.Peer-Reviewed Original ResearchConceptsAPAP-protein adductsAcetaminophen useCirrhosis groupClinical outcomesDay 5Sensitive biomarkerAdverse clinical outcomesShort-term administrationCompensated cirrhosisLiver injuryAPAP administrationLiver damagePK analysisCurrent guidelinesStudy initiationCirrhosisTerm safetyDay 1Day 3APAP metabolitesHigh dosesPatientsPilot studyAPAPLonger treatment
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
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 cellsAn 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
2015
Strategies 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 AssociationBeyond 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 StatementsIntegrins, 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
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
2009
Transcriptional 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
2008
Adenosine induces loss of actin stress fibers and inhibits contraction in hepatic stellate cells via Rho inhibition
Sohail MA, Hashmi AZ, Hakim W, Watanabe A, Zipprich A, Groszmann RJ, Dranoff JA, Torok NJ, Mehal WZ. Adenosine induces loss of actin stress fibers and inhibits contraction in hepatic stellate cells via Rho inhibition. Hepatology 2008, 49: 185-194. PMID: 18844235, PMCID: PMC3129263, DOI: 10.1002/hep.22589.Peer-Reviewed Original ResearchIL-6 downregulates transcription of NTPDase2 via specific promoter elements
Yu J, Lavoie E, Sheung N, Tremblay JJ, Sévigny J, Dranoff JA. IL-6 downregulates transcription of NTPDase2 via specific promoter elements. AJP Gastrointestinal And Liver Physiology 2008, 294: g748-g756. PMID: 18202114, PMCID: PMC5239663, DOI: 10.1152/ajpgi.00208.2007.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphatasesAnimalsBlotting, WesternCell DifferentiationCloning, MolecularCytokine Receptor gp130DNA, ComplementaryDown-RegulationElectrophoretic Mobility Shift AssayFibroblastsFluorescent Antibody TechniqueInterleukin-6LuciferasesMaleMicroscopy, ConfocalMutagenesis, Site-DirectedPromoter Regions, GeneticRatsRats, Sprague-DawleyResponse ElementsReverse Transcriptase Polymerase Chain ReactionConceptsBile ductular proliferationPortal fibroblastsIL-6Ductular proliferationBiliary cirrhosisIL-6 receptor gp80Alpha-smooth muscle actin expressionIL-6 responsePotential therapeutic approachMuscle actin expressionNTPDase2 expressionTime-dependent fashionBiliary fibrosisIL-6 receptor gp130Interleukin-6Therapeutic approachesResponse elementMyofibroblastic differentiationDiphosphohydrolase 2CirrhosisMRNA expressionActin expressionMinimal promoter constructProtein expressionIL-6 response element
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
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