2024
Portal Fibrosis and the Ductular Reaction: Pathophysiological Role in the Progression of Liver Disease and Translational Opportunities
Gupta V, Sehrawat T, Pinzani M, Strazzabosco M. Portal Fibrosis and the Ductular Reaction: Pathophysiological Role in the Progression of Liver Disease and Translational Opportunities. Gastroenterology 2024 PMID: 39251168, DOI: 10.1053/j.gastro.2024.07.044.Peer-Reviewed Original ResearchLiver diseasePortal fibrosisDuctular reactionPathological repairProgression of liver diseaseCholestatic liver diseaseTranslational opportunitiesChronic liver diseaseProgression of fibrosisCell typesChronic human liver diseaseHuman liver diseaseTumor microenvironmentTherapeutic advancesImmune modulationHistological abnormalitiesVascular changesLiver repairPathophysiological roleFibrosisTreatment prospectsPortal spacesMesenchymal cellsVascular cellsComplex crosstalk
2021
The Neglected Role of Bile Duct Epithelial Cells in NASH
Cadamuro M, Lasagni A, Sarcognato S, Guido M, Fabris R, Strazzabosco M, Strain AJ, Simioni P, Villa E, Fabris L. The Neglected Role of Bile Duct Epithelial Cells in NASH. Seminars In Liver Disease 2021, 42: 034-047. PMID: 34794182, DOI: 10.1055/s-0041-1739455.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseNonalcoholic steatohepatitisLiver diseaseInsulin resistancePrevalent liver diseaseBile duct epithelial cellsFatty liver diseaseSubset of patientsCommon pathogenetic mechanismDuct epithelial cellsMultiple biological effectsFibro-inflammationHepatic manifestationNAFLD patientsPortal fibrosisMetabolic syndromeBile ductDuctular reactionDisease progressionPathogenetic mechanismsLiver cancerMetabolic alterationsProgenitor cell compartmentEpithelial cellsDisease
2020
Liver Matrix in Benign and Malignant Biliary Tract Disease
Fabris L, Cadamuro M, Cagnin S, Strazzabosco M, Gores G. Liver Matrix in Benign and Malignant Biliary Tract Disease. Seminars In Liver Disease 2020, 40: 282-297. PMID: 32162285, DOI: 10.1055/s-0040-1705109.Peer-Reviewed Original ResearchConceptsMalignant biliary tract diseasesBiliary tract diseaseExtracellular matrixReactive ductular cellsPro-oncogenic effectsHepatic progenitor cellsExtracellular matrix undergoesBiliary repairDuctular reactionTract diseaseBiliary damageMalignant transformationResident cellsDuctular cellsMain molecular factorsProgenitor cellsMolecular factorsMechanical signalsLiver matrixNoncollagenous glycoproteinsStructural alterationsDirect interactionBiochemical compositionCellsMultifunctional molecules
2017
Notch signaling and progenitor/ductular reaction in steatohepatitis
Morell CM, Fiorotto R, Meroni M, Raizner A, Torsello B, Cadamuro M, Spagnuolo G, Kaffe E, Sutti S, Albano E, Strazzabosco M. Notch signaling and progenitor/ductular reaction in steatohepatitis. PLOS ONE 2017, 12: e0187384. PMID: 29140985, PMCID: PMC5687773, DOI: 10.1371/journal.pone.0187384.Peer-Reviewed Original ResearchConceptsHepatic stellate cellsDuctular reactionRole of NotchMCD diet-fed miceMethionine-choline deficient (MCD) dietHepatic progenitor cell activationPrimary hepatic stellate cellsChronic liver diseaseDiet-fed miceTGF-β1 expressionAlternative therapeutic targetsTGF-β1 treatmentProgenitor cell activationNotch-1 activationLiver injuryMCD dietLiver diseaseFibrosis progressionNotch signalingDR responseLiver repairBSEP expressionHepatocyte cell lineLiver cancerAAV8-TBGAnimal models of biliary injury and altered bile acid metabolism
Mariotti V, Strazzabosco M, Fabris L, Calvisi DF. Animal models of biliary injury and altered bile acid metabolism. Biochimica Et Biophysica Acta (BBA) - Molecular Basis Of Disease 2017, 1864: 1254-1261. PMID: 28709963, PMCID: PMC5764833, DOI: 10.1016/j.bbadis.2017.06.027.Peer-Reviewed Original ResearchConceptsBile acid metabolismBiliary injuryMouse modelAnimal modelsDistinct immune systemCholestatic liver injuryAcid metabolismJesus BanalesMarco MarzioniNicholas LaRussoPeter JansenBiliary repairLiver injuryDuctular reactionLiver repairObstructive cholestasisDisease progressionPeribiliary inflammationMain phenotypic featuresBiliary dysgenesisViral infectionImmune systemLiver homeostasisLiver phenotypeHuman setting
2016
Revisiting Epithelial‐to‐Mesenchymal Transition in Liver Fibrosis: Clues for a Better Understanding of the “Reactive” Biliary Epithelial Phenotype
Fabris L, Brivio S, Cadamuro M, Strazzabosco M. Revisiting Epithelial‐to‐Mesenchymal Transition in Liver Fibrosis: Clues for a Better Understanding of the “Reactive” Biliary Epithelial Phenotype. Stem Cells International 2016, 2016: 2953727. PMID: 26880950, PMCID: PMC4736590, DOI: 10.1155/2016/2953727.Peer-Reviewed Original ResearchDuctular reactive cellsDuctular reactionHepatic progenitor cell compartmentMesenchymal transitionBiliary epithelial phenotypeChronic biliary damageSevere hepatic disordersBile duct epithelial cellsEpithelial cellsLiver disease progressionDuct epithelial cellsNew antifibrotic therapiesPortal fibrosisInflammatory cellsLiver fibrosisAntifibrotic therapyBiliary damageDisease progressionHepatic disordersEMT changesReactive cellsMesenchymal markersHepatic scarringProgenitor cell compartmentCholangiopathy
2014
Osteopontin: a new player in regulating hepatic ductular reaction and hepatic progenitor cell responses during chronic liver injury
Strazzabosco M, Fabris L, Albano E. Osteopontin: a new player in regulating hepatic ductular reaction and hepatic progenitor cell responses during chronic liver injury. Gut 2014, 63: 1693. PMID: 25056656, PMCID: PMC4519840, DOI: 10.1136/gutjnl-2014-307712.Peer-Reviewed Original Research
2013
Notch 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
Development of the bile ducts: Essentials for the clinical hepatologist
Strazzabosco M, Fabris L. Development of the bile ducts: Essentials for the clinical hepatologist. Journal Of Hepatology 2012, 56: 1159-1170. PMID: 22245898, PMCID: PMC3328609, DOI: 10.1016/j.jhep.2011.09.022.Peer-Reviewed Original ResearchConceptsLiver diseaseBile ductBiliary structuresFibropolycystic liver diseaseExtrahepatic biliary treeBiliary developmentLiver repair mechanismsHepatocellular damageBiliary treeDuctular reactionLiver repairReparative responseAlagille syndromePathogenic aspectsClinical hepatologistsCholangiopathyGrowth factorParacrine signalsEmbryonic lifeDiseaseDuctRepair mechanismsHepatologistsSyndromeTranscription factors
2011
Loss of CFTR Affects Biliary Epithelium Innate Immunity and Causes TLR4–NF-κB—Mediated Inflammatory Response in Mice
Fiorotto R, Scirpo R, Trauner M, Fabris L, Hoque R, Spirli C, Strazzabosco M. Loss of CFTR Affects Biliary Epithelium Innate Immunity and Causes TLR4–NF-κB—Mediated Inflammatory Response in Mice. Gastroenterology 2011, 141: 1498-1508.e5. PMID: 21712022, PMCID: PMC3186841, DOI: 10.1053/j.gastro.2011.06.052.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-Bacterial AgentsBile DuctsCholagogues and CholereticsCholangitisColitisCytokinesDextran SulfateDisease Models, AnimalEpithelial CellsHEK293 CellsHumansImmunity, InnateInflammation MediatorsKeratin-19Leukocyte Common AntigensLipopolysaccharidesMiceMice, Inbred C57BLMice, Inbred CFTRMice, KnockoutNeomycinNF-kappa BPhosphorylationPolymyxin BSrc-Family KinasesTime FactorsToll-Like Receptor 4TransfectionUrsodeoxycholic AcidConceptsCFTR KO miceBiliary epitheliumCystic fibrosisPortal inflammationBiliary damageInflammatory responseInnate immunityGut-derived bacterial productsTLR4 inhibitor TAK-242Toll-like receptor 4Cystic fibrosis transmembrane conductance regulatorInhibitor TAK-242Wild-type littermatesActivation of NFNuclear factor κBOral neomycinTLR4-NFTAK-242Liver damagePathogenetic roleBile flowDuctular reactionReceptor 4Cytokine secretionUrsodeoxycholic acid
2010
Insulin resistance and necroinflammation drives ductular reaction and epithelial-mesenchymal transition in chronic hepatitis C
Svegliati-Baroni G, Faraci G, Fabris L, Saccomanno S, Cadamuro M, Pierantonelli I, Trozzi L, Bugianesi E, Guido M, Strazzabosco M, Benedetti A, Marchesini G. Insulin resistance and necroinflammation drives ductular reaction and epithelial-mesenchymal transition in chronic hepatitis C. Gut 2010, 60: 108. PMID: 20966027, PMCID: PMC3784835, DOI: 10.1136/gut.2010.219741.Peer-Reviewed Original ResearchConceptsChronic hepatitis CFibroblast-specific protein-1Epithelial-mesenchymal transitionInsulin resistanceDuctular reactionHepatitis CHepatic fibrosisEpithelial componentOral glucose insulin sensitivityOral glucose tolerance testTertiary care academic centerEpithelial-mesenchymal transition (EMT) markersNuclear Snail expressionProspective observational studyGlucose insulin sensitivityGlucose tolerance testDegree of necroinflammationStage of fibrosisTissue repairCK7-positive cellsNecroinflammatory activityNecroinflammatory scoreAdvanced fibrosisConsecutive patientsTotal inflammation