2017
Extracellular 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
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
2008
IL-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 inhibitorsDesminMyofibroblastsFibroblastsCells
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 evidencePortal Fibroblasts Regulate the Proliferation of Bile Duct Epithelia via Expression of NTPDase2*
Jhandier MN, Kruglov EA, Lavoie É, Sévigny J, Dranoff JA. Portal Fibroblasts Regulate the Proliferation of Bile Duct Epithelia via Expression of NTPDase2*. Journal Of Biological Chemistry 2005, 280: 22986-22992. PMID: 15799977, DOI: 10.1074/jbc.m412371200.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphatasesAnimalsBile DuctsBromodeoxyuridineCell ProliferationCholangiocarcinomaCholestasisCoculture TechniquesDNA, ComplementaryEpithelial CellsFibroblastsHumansLiverMaleMicroscopy, ConfocalMicroscopy, FluorescenceModels, BiologicalRatsRats, Sprague-DawleyReverse Transcriptase Polymerase Chain ReactionRNA, Small InterferingSignal TransductionTransfectionConceptsBile ductular proliferationExpression of NTPDase2Portal fibroblastsDuctular proliferationBile duct epitheliumNTPDase2 expressionMz-ChA-1 cellsPortal myofibroblastsP2Y receptorsDuct epitheliumBile duct-ligated ratsCell proliferationDuct-ligated ratsReal-time reverse transcription PCRQuantitative real-time reverse transcription PCRHuman cholangiocarcinoma cellsNovel co-culture modelMz-ChA-1 human cholangiocarcinoma cellsNucleotidase apyraseP2Y activationCo-culture modelObstructive cholestasisReverse transcription-PCRPathologic alterationsEpithelial proliferation
2004
Autocrine 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
The ecto‐nucleoside triphosphate diphosphohydrolase NTPDase2/CD39L1 is expressed in a novel functional compartment within the liver
Dranoff JA, Kruglov EA, Robson SC, Braun N, Zimmermann H, Sévigny J. The ecto‐nucleoside triphosphate diphosphohydrolase NTPDase2/CD39L1 is expressed in a novel functional compartment within the liver. Hepatology 2002, 36: 1135-1144. PMID: 12395323, DOI: 10.1053/jhep.2002.36823.Peer-Reviewed Original ResearchConceptsIntrahepatic bile ductsExtracellular nucleotidesBile ductDiverse biological functionsBlot analysisEcto-nucleoside triphosphate diphosphohydrolasesNTPDase2/CD39L1Portal fibroblastsNorthern blot analysisCellular compartmentsBiological functionsPotential regulatorConfocal immunofluorescenceWestern blot analysisHepatic blood flowBile duct epitheliumReverse transcription-polymerase chain reactionFunctional assaysTriphosphate diphosphohydrolasesImmunoelectron microscopyFunctional compartmentsHepatic central veinNucleotidesNTPDase1NTPDase2Isolation 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