2024
Heterogeneity of hepatocyte dynamics restores liver architecture after chemical, physical or viral damage
Ruz-Maldonado I, Gonzalez J, Zhang H, Sun J, Bort A, Kabir I, Kibbey R, Suárez Y, Greif D, Fernández-Hernando C. Heterogeneity of hepatocyte dynamics restores liver architecture after chemical, physical or viral damage. Nature Communications 2024, 15: 1247. PMID: 38341404, PMCID: PMC10858916, DOI: 10.1038/s41467-024-45439-0.Peer-Reviewed Original Research
2020
Stem Cells and Hydrogels for Liver Tissue Engineering: Synergistic Cure for Liver Regeneration
Nadi A, Moradi L, Ai J, Asadpour S. Stem Cells and Hydrogels for Liver Tissue Engineering: Synergistic Cure for Liver Regeneration. Stem Cell Reviews And Reports 2020, 16: 1092-1104. PMID: 33070256, DOI: 10.1007/s12015-020-10060-3.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsClinical Trials as TopicHumansHydrogelsLiverLiver RegenerationStem CellsTissue EngineeringImproving the Safety of Major Resection for Hepatobiliary Malignancy: Portal Vein Embolization and Recent Innovations in Liver Regeneration Strategies
Madoff DC, Odisio BC, Schadde E, Gaba RC, Bennink RJ, van Gulik TM, Guiu B. Improving the Safety of Major Resection for Hepatobiliary Malignancy: Portal Vein Embolization and Recent Innovations in Liver Regeneration Strategies. Current Oncology Reports 2020, 22: 59. PMID: 32415401, DOI: 10.1007/s11912-020-00922-x.Peer-Reviewed Original ResearchMeSH KeywordsBiliary Tract NeoplasmsEmbolization, TherapeuticHepatectomyHumansLiverLiver NeoplasmsLiver RegenerationPortal VeinPreoperative CareConceptsPortal vein embolizationFuture liver remnantFLR hypertrophyMajor hepatectomyVein embolizationHepatobiliary malignanciesCT volumetryAppropriate surgical candidatesExtent of resectionPortal vein ligationRadiation lobectomyVenous deprivationMajor resectionPerformance statusSurgical candidatesComplication rateLiver diseaseVein ligationLiver partitionLiver remnantTumor typesPhysiological imagingResectionEmbolizationMalignancyBile canaliculi remodeling activates YAP via the actin cytoskeleton during liver regeneration
Meyer K, Morales‐Navarrete H, Seifert S, Wilsch‐Braeuninger M, Dahmen U, Tanaka E, Brusch L, Kalaidzidis Y, Zerial M. Bile canaliculi remodeling activates YAP via the actin cytoskeleton during liver regeneration. Molecular Systems Biology 2020, 16: msb198985. PMID: 32090478, PMCID: PMC7036714, DOI: 10.15252/msb.20198985.Peer-Reviewed Original ResearchConceptsActin cytoskeletonActive YAPMechanisms of organ size controlF-actin-rich regionsTranscriptional co-activator YAPSurface of hepatocytesOrgan size controlCo-activator YAPApical surface of hepatocytesApical surfaceF-actinAcid fluctuationsHippo signalingTissue homeostasisBile acidsMouse liver regenerationBile acid overloadYAPMechano-sensory systemsCytoskeletonAcid overloadActinBile canalicular networkLevels of bile acidsCanalicular network
2019
Expression of the type 3 InsP3 receptor is a final common event in the development of hepatocellular carcinoma
Guerra MT, Florentino RM, Franca A, Lima Filho AC, Dos Santos ML, Fonseca RC, Lemos FO, Fonseca MC, Kruglov E, Mennone A, Njei B, Gibson J, Guan F, Cheng YC, Ananthanarayanan M, Gu J, Jiang J, Zhao H, Lima CX, Vidigal PT, Oliveira AG, Nathanson MH, Leite MF. Expression of the type 3 InsP3 receptor is a final common event in the development of hepatocellular carcinoma. Gut 2019, 68: 1676-1687. PMID: 31315892, PMCID: PMC7087395, DOI: 10.1136/gutjnl-2018-317811.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsApoptosisCalcium SignalingCarcinogenesisCarcinoma, HepatocellularCell ProliferationCells, CulturedDNA MethylationFemaleGene Expression Regulation, NeoplasticHepatocytesHumansInositol 1,4,5-Trisphosphate ReceptorsLiverLiver NeoplasmsLiver RegenerationMaleMice, KnockoutMiddle AgedSurvival AnalysisConceptsChronic liver diseaseITPR3 expressionLiver cancer cellsLiver diseaseMouse modelFinal common eventCancer cellsSpecimens of patientsIndependent patient cohortsControl liver specimensHuman HCC cellsType 3 InsP3 receptorHuman liver samplesIncreased expression levelCancer deathPatient cohortCommon molecular eventPoor survivalHepatocellular carcinomaLiver specimensNormal liverHCC cellsAbstractTextHCCType 3 isoformCholangiocyte pathobiology
Banales JM, Huebert RC, Karlsen T, Strazzabosco M, LaRusso NF, Gores GJ. Cholangiocyte pathobiology. Nature Reviews Gastroenterology & Hepatology 2019, 16: 269-281. PMID: 30850822, PMCID: PMC6563606, DOI: 10.1038/s41575-019-0125-y.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityBile Duct DiseasesBile DuctsEpithelial CellsFibrosisHumansImmunity, InnateInflammationLiver FailureLiver RegenerationConceptsCholangiocyte pathobiologyNew disease-modifying therapiesLiver regenerationRole of cholangiocytesAdvanced liver failureDisease-modifying therapiesExtrahepatic bile ductChronic disease statesAdaptive immune responsesReactive ductular cellsLiver failureBiliary tractLiver diseaseBile ductBile productionImmune responseHepatocyte regenerationImmune systemDuctular cellsCholangiopathyDisease statesCholangiocytesEpithelial cellsAnatomic nicheRepair response
2018
Nonalcoholic fatty liver disease impairs expression of the type II inositol 1,4,5‐trisphosphate receptor
Khamphaya T, Chukijrungroat N, Saengsirisuwan V, Mitchell‐Richards K, Robert ME, Mennone A, Ananthanarayanan M, Nathanson MH, Weerachayaphorn J. Nonalcoholic fatty liver disease impairs expression of the type II inositol 1,4,5‐trisphosphate receptor. Hepatology 2018, 67: 560-574. PMID: 29023819, PMCID: PMC5893412, DOI: 10.1002/hep.29588.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseImpaired liver regenerationNonalcoholic steatohepatitisLiver regenerationHuh7 cellsLiver diseaseEffect of NAFLDPrevalent liver diseaseFatty liver diseaseC-JunHigh-fructose dietLiver biopsy specimensCell proliferationCalcium signalingHepG2 cellsLiver of ratsCell nuclear antigenCalcium release channelSimple steatosisLiver biopsyFatty liverTrisphosphate receptorBiopsy specimensRat modelType II inositol
2017
Catheter-directed Intraportal Delivery of Endothelial Cell Therapy for Liver Regeneration: A Feasibility Study in a Large-Animal Model of Cirrhosis.
Lee KS, Santagostino SF, Li D, Ramjit A, Serrano K, Ginsberg MD, Ding BS, Rafii S, Madoff DC. Catheter-directed Intraportal Delivery of Endothelial Cell Therapy for Liver Regeneration: A Feasibility Study in a Large-Animal Model of Cirrhosis. Radiology 2017, 285: 114-123. PMID: 28498793, DOI: 10.1148/radiol.2017162617.Peer-Reviewed Original ResearchConceptsEndothelial cell therapyMean proliferation indexLiver endothelial cellsCell therapyEndothelial cellsIntraportal deliveryProliferation indexPorcine modelCatheter-directed deliveryTreatment of cirrhosisInduction of cirrhosisMasson's trichrome stainingUnpaired t-testLarge animal studiesAutologous cell therapyHepatic specimensHepatobiliary injuryTranscatheter infusionHepatic arteryFluorescence-activated cellPathologic examinationHepatic fibrosisDuctal damageLiver fibrosisSurrogate marker
2016
Ductular reactions in the liver regeneration process with local inflammation after physical partial hepatectomy
Suzuki Y, Katagiri H, Wang T, Kakisaka K, Kume K, Nishizuka SS, Takikawa Y. Ductular reactions in the liver regeneration process with local inflammation after physical partial hepatectomy. Laboratory Investigation 2016, 96: 1211-1222. PMID: 27617400, DOI: 10.1038/labinvest.2016.97.Peer-Reviewed Original ResearchConceptsLiver regeneration processDuctular reactionMurine liver injury modelsLocal inflammatory responseLiver injury modelExtracellular matrix-associated genesPartial hepatectomy modelMatrix-associated genesStem/progenitor cellsLiver stem/progenitor cellsTissue repair processLiver regeneration studiesSystematic remodelingExtracellular matrix remodelingLeft lobeInflammatory cytokinesLocal inflammationLiver weightHepatocyte hypertrophyInflammatory responseInjury modelLocal injuryKi67 stainingSurgical proceduresEntire liverAkt‐mediated foxo1 inhibition is required for liver regeneration
Pauta M, Rotllan N, Fernández-Hernando A, Langhi C, Ribera J, Lu M, Boix L, Bruix J, Jimenez W, Suárez Y, Ford DA, Baldán A, Birnbaum MJ, Morales-Ruiz M, Fernández-Hernando C. Akt‐mediated foxo1 inhibition is required for liver regeneration. Hepatology 2016, 63: 1660-1674. PMID: 26473496, PMCID: PMC5177729, DOI: 10.1002/hep.28286.Peer-Reviewed Original ResearchConceptsAkt/protein kinase BCellular eventsProtein kinase BAkt2-deficient miceAbsence of Akt1Lipid droplet formationContribution of AktAkt2-null miceLiver regenerationAbnormal cellular eventsTranscription factorsAKT-FOXO1Kinase BLiver-specific deletionSuccessful liver regenerationPartial hepatectomyHepatic regenerative capabilityAKT1Chronic liver diseaseFOXO1 inhibitionCell proliferationEssential roleImpaired liver regenerationIntracellular mediatorsEfficient liver regeneration
2015
A Distinct Subpopulation of Bone Marrow Mesenchymal Stem Cells, Muse Cells, Directly Commit to the Replacement of Liver Components
Katagiri H, Kushida Y, Nojima M, Kuroda Y, Wakao S, Ishida K, Endo F, Kume K, Takahara T, Nitta H, Tsuda H, Dezawa M, Nishizuka SS. A Distinct Subpopulation of Bone Marrow Mesenchymal Stem Cells, Muse Cells, Directly Commit to the Replacement of Liver Components. American Journal Of Transplantation 2015, 16: 468-483. PMID: 26663569, DOI: 10.1111/ajt.13537.Peer-Reviewed Original ResearchConceptsLiver componentsBone marrow mesenchymal stem cellsMarrow mesenchymal stem cellsLiver regenerationBM-MSCsMuse cellsMesenchymal stem cellsLiving-donor liver transplantationSinusoidal endothelial cellsMultilineage-differentiating stress-enduring (Muse) cellsPartial hepatectomy modelStem cellsGraft liverLiver transplantationPolymerase chain reactionCell involvementImmunodeficient miceKupffer cellsSinusoidal cellsPeriportal areasExtrahepatic originHepatectomy modelSpecific subpopulationsEndothelial cellsProgenitor markersEmerging roles of Notch signaling in liver disease
Geisler F, Strazzabosco M. Emerging roles of Notch signaling in liver disease. Hepatology 2015, 61: 382-392. PMID: 24930574, PMCID: PMC4268103, DOI: 10.1002/hep.27268.Peer-Reviewed Original ResearchConceptsRole of NotchNotch signalingMammalian cell fateSpecific cellular contextCell fateCellular contextOrgan homeostasisStem cell featuresSignificance of NotchDistinct liver cell typesLiver developmentLiver cell typesCell typesLiver diseaseIntrahepatic cholangiocarcinomaLiver malignanciesHepatocellular carcinomaFurther cellHomeostasisLiver homeostasisLiver metabolismPersistent activationClinical practiceRepair processSignaling
2014
Neural cell adhesion molecule and polysialic acid in ductular reaction: The puzzle is far from completed, but the picture is becoming more clear
Strazzabosco M, Fabris L. Neural cell adhesion molecule and polysialic acid in ductular reaction: The puzzle is far from completed, but the picture is becoming more clear. Hepatology 2014, 60: 1469-1472. PMID: 24995463, PMCID: PMC4520409, DOI: 10.1002/hep.27291.Peer-Reviewed Original Research
2013
Notch signaling and new therapeutic options in liver disease
Morell CM, Strazzabosco M. Notch signaling and new therapeutic options in liver disease. Journal Of Hepatology 2013, 60: 885-890. PMID: 24308992, DOI: 10.1016/j.jhep.2013.11.028.Peer-Reviewed Original ResearchConceptsLiver diseaseTherapeutic agentsNew therapeutic optionsNotch signalingSpecific therapeutic agentsStem cell featuresTherapeutic optionsLiver malignanciesLiver metabolismTherapeutic relevanceAberrant activationLiver regenerationPersistent activationDiseaseAdult liverPossible targetsFurther studiesCell featuresNovel findingsRecent reportsNotch pathwayLiverCritical playersSignalingActivationThe insulin receptor translocates to the nucleus to regulate cell proliferation in liver
Amaya MJ, Oliveira AG, Guimarães ES, Casteluber MC, Carvalho SM, Andrade LM, Pinto MC, Mennone A, Oliveira CA, Resende RR, Menezes GB, Nathanson MH, Leite MF. The insulin receptor translocates to the nucleus to regulate cell proliferation in liver. Hepatology 2013, 59: 274-283. PMID: 23839970, PMCID: PMC3823683, DOI: 10.1002/hep.26609.Peer-Reviewed Original ResearchConceptsInsulin's metabolic effectsInsulin's mitogenic effectsInsulin receptorCell proliferationMitogenic effectMetabolic effectsInsulin-induced increaseFormation of inositolHepatic glucose metabolismInsulin's abilityFormation of InsP3Potential targetPathwayTherapeutic modulationGlucose metabolismProliferationInsP3Partial hepatectomyHepatic mitogenLiver growthLiver regenerationNucleusClathrinReceptorsLiverVascular biology of the biliary epithelium
Morell CM, Fabris L, Strazzabosco M. Vascular biology of the biliary epithelium. Journal Of Gastroenterology And Hepatology 2013, 28: 26-32. PMID: 23855292, PMCID: PMC3721432, DOI: 10.1111/jgh.12022.Peer-Reviewed Original ResearchMeSH KeywordsAngiopoietinsAnimalsAutocrine CommunicationBile Duct DiseasesBile Ducts, IntrahepaticEpithelial CellsEpitheliumHumansLiverLiver Diseases, AlcoholicLiver RegenerationNeovascularization, PathologicParacrine CommunicationPlatelet-Derived Growth FactorRatsSignal TransductionVascular Endothelial Growth Factor AConceptsBile ductIntrahepatic bile ductsHepatic arteryPeribiliary plexusUnderlying molecular mechanismsArterial supplyLiver repairNormal organ physiologyLiver pathophysiologyVascular cell typesPathophysiological settingsVascular structuresStrong associationVascular biologyDifferent vascular cell typesCholangiocytesAngiogenic signalsLiver developmentCell typesMolecular mechanismsOrgan physiologyDuctAssociationCross talkNotch signalling beyond liver development: Emerging concepts in liver repair and oncogenesis
Morell CM, Fiorotto R, Fabris L, Strazzabosco M. Notch signalling beyond liver development: Emerging concepts in liver repair and oncogenesis. Clinics And Research In Hepatology And Gastroenterology 2013, 37: 447-454. PMID: 23806629, DOI: 10.1016/j.clinre.2013.05.008.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAnimalsBile Duct NeoplasmsBiliary TractCalcium-Binding ProteinsCarcinogenesisCarcinoma, HepatocellularCholangiocarcinomaHepatocytesHumansIntercellular Signaling Peptides and ProteinsJagged-1 ProteinLiverLiver NeoplasmsLiver RegenerationMembrane ProteinsReceptor Cross-TalkReceptors, NotchSerrate-Jagged ProteinsSignal TransductionReticulon 4B (Nogo‐B) facilitates hepatocyte proliferation and liver regeneration in mice
Gao L, Utsumi T, Tashiro K, Liu B, Zhang D, Swenson ES, Iwakiri Y. Reticulon 4B (Nogo‐B) facilitates hepatocyte proliferation and liver regeneration in mice. Hepatology 2013, 57: 1992-2003. PMID: 23299899, PMCID: PMC3628958, DOI: 10.1002/hep.26235.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell ProliferationEpidermal Growth FactorHepatectomyHepatocyte Growth FactorHepatocytesInterleukin-6LiverLiver RegenerationMaleMiceMice, Inbred C57BLMice, KnockoutModels, AnimalMyelin ProteinsNogo ProteinsSignal TransductionSTAT3 Transcription FactorTime FactorsTransforming Growth Factor betaConceptsHepatocyte growth factorRole of NogoInterleukin-6Hepatocyte proliferationLiver regenerationEpidermal growth factorReticulon 4BTGF-β1Growth factorKi67 labeling indexB knockout miceHepatic stellate cellsReal-time polymerase chain reactionQuantitative real-time polymerase chain reactionIL-6/signal transducerGrowth factor βTime-dependent mannerRemnant liverKO miceLiver fibrosisPolymerase chain reactionInhibitor of DNAStellate cellsKnockout miceLabeling indexNotch signaling regulates tubular morphogenesis during repair from biliary damage in mice
Fiorotto R, Raizner A, Morell CM, Torsello B, Scirpo R, Fabris L, Spirli C, Strazzabosco M. Notch signaling regulates tubular morphogenesis during repair from biliary damage in mice. Journal Of Hepatology 2013, 59: 124-130. PMID: 23500150, PMCID: PMC3777645, DOI: 10.1016/j.jhep.2013.02.025.Peer-Reviewed Original ResearchMeSH Keywords1-NaphthylisothiocyanateAmyloid Precursor Protein SecretasesAnimalsBile Ducts, IntrahepaticCalcium-Binding ProteinsImmunoglobulin J Recombination Signal Sequence-Binding ProteinIntercellular Signaling Peptides and ProteinsJagged-1 ProteinLiver RegenerationMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutMorphogenesisPyridinesReceptor, Notch2RNA, Small InterferingSerrate-Jagged ProteinsSignal TransductionStem CellsConceptsWild-type miceHepatic progenitor cellsBiliary damageType miceProgenitor cellsDuctular reactionΓ-secretase inhibitor treatmentTubule formationNotch signalingNotch-2 receptorRBP-JkBiliary repairMature ductsLiver-specific defectCKO miceInhibitor treatmentAbstractTextMiceNotch inhibitionNotch-1Jagged-1Notch-2ANITAIMSSOX-9
2012
Mir-33 regulates cell proliferation and cell cycle progression
Cirera-Salinas D, Pauta M, Allen RM, Salerno AG, Ramírez CM, Chamorro-Jorganes A, Wanschel AC, Lasuncion MA, Morales-Ruiz M, Suarez Y, Baldan A, Esplugues E, Fernández-Hernando C. Mir-33 regulates cell proliferation and cell cycle progression. Cell Cycle 2012, 11: 922-933. PMID: 22333591, PMCID: PMC3323796, DOI: 10.4161/cc.11.5.19421.Peer-Reviewed Original ResearchConceptsCell cycle progressionCyclin-dependent kinase 6Cycle progressionCell proliferationCell cycle regulationMiR-33Expression of genesCyclin D1Cell cycle arrestSREBP genesCycle regulationFatty acid metabolismHost genesPosttranscriptional levelGene expressionIntronic sequencesKinase 6Cellular growthCritical regulatorCycle arrestCellular levelLiver regenerationGenesMiR-33 expressionAcid metabolism
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