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
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
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