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 cellsDiseaseNew insights on the role of vascular endothelial growth factor in biliary pathophysiology
Mariotti V, Fiorotto R, Cadamuro M, Fabris L, Strazzabosco M. New insights on the role of vascular endothelial growth factor in biliary pathophysiology. JHEP Reports 2021, 3: 100251. PMID: 34151244, PMCID: PMC8189933, DOI: 10.1016/j.jhepr.2021.100251.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsVEGF/VEGFRCell biologyVascular endothelial growth factorCritical biological processesEpithelial cell biologyHIF1α-dependent mechanismEndothelial cell biologyEndothelial growth factorEpithelial cellsGrowth factorAccessory proteinsLiver repair processesCystic cellsBiological processesKinase receptorsVEGFR-2 receptorCell typesRole of VEGFBiliary developmentBiliary pathophysiologyDevelopment of cirrhosisChronic biliary diseaseBile duct proliferationPolycystic liver diseaseWound healing response
2020
Cholangiocyte Biology and Pathobiology
Cadamuro M, Fiorotto R, Strazzabosco M. Cholangiocyte Biology and Pathobiology. 2020, 391-407. DOI: 10.1002/9781119436812.ch32.ChaptersBiliary treeEpithelial cellsProliferation of cholangiocytesAmpulla of VaterExtrahepatic biliary treeEpithelial innate immunityToll-like receptorsCanals of HeringBiliary epithelial cellsIntrahepatic branchesLiver damageBiliary systemLiver insultEpithelial barrierInnate immunityCholangiocytesNormal homeostasisLiver lobuleNuclear receptorsCholangiocyte biologyReceptorsCellsVaterMajor roleInsult
2019
Cholangiocyte 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 ResearchConceptsCholangiocyte 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
2017
The deleterious interplay between tumor epithelia and stroma in cholangiocarcinoma
Cadamuro M, Stecca T, Brivio S, Mariotti V, Fiorotto R, Spirli C, Strazzabosco M, Fabris L. The deleterious interplay between tumor epithelia and stroma in cholangiocarcinoma. Biochimica Et Biophysica Acta (BBA) - Molecular Basis Of Disease 2017, 1864: 1435-1443. PMID: 28757170, PMCID: PMC6386155, DOI: 10.1016/j.bbadis.2017.07.028.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsTumor reactive stromaReactive stromaMain cellular componentsDeleterious interplayCyto/chemokinesCellular componentsParacrine signalsPrognosis of cholangiocarcinomaTumor epithelial cellsCell interactionsEarly invasivenessJesus BanalesMarco MarzioniNicholas LaRussoPeter JansenDifferent cell elementsEpithelial cellsEpithelial malignanciesTumor behaviorTumor epitheliumGrowth factorNeoplastic cellsTumor progressionCentral roleStromal componentsThe Healthy Biliary Tree: Cellular and Immune Biology
Cadamuro M, Fabris L, Strazzabosco M. The Healthy Biliary Tree: Cellular and Immune Biology. 2017, 17-41. DOI: 10.1007/978-3-319-50168-0_2.Peer-Reviewed Original ResearchBiliary innate immunityToll-like receptorsPathogen-associated molecular patternsBiliary treeLiver diseaseCystic fibrosis-related liver diseaseInnate immunityCystic fibrosis liver diseaseAntigen-presenting cellsBiliary epithelial cellsLiver injuryBile ductBiliary diseaseLiver damageInflammatory responseImmune biologyFirst defense lineProinflammatory behaviorSecretory activityMolecular patternsCholangiocytesEpithelial cellsDiseaseCholangiopathyEvidence highlights
2016
The cystic fibrosis transmembrane conductance regulator controls biliary epithelial inflammation and permeability by regulating Src tyrosine kinase activity
Fiorotto R, Villani A, Kourtidis A, Scirpo R, Amenduni M, Geibel PJ, Cadamuro M, Spirli C, Anastasiadis PZ, Strazzabosco M. The cystic fibrosis transmembrane conductance regulator controls biliary epithelial inflammation and permeability by regulating Src tyrosine kinase activity. Hepatology 2016, 64: 2118-2134. PMID: 27629435, PMCID: PMC5115965, DOI: 10.1002/hep.28817.Peer-Reviewed Original ResearchConceptsBiliary epithelial cellsLiver diseaseToll-like receptor 4 activityToll-like receptor 4 responsesCystic fibrosis transmembrane conductance regulatorToll-like receptor 4Nuclear factorEpithelial cellsProinflammatory cytokine productionNovel therapeutic targetEpithelial barrier functionActivated B cellsFibrosis transmembrane conductance regulatorTransmembrane conductance regulatorCytokine productionEpithelial inflammationInflammatory cellsInflammatory processReceptor 4Biliary damageInflammatory responseInflammatory cholangiopathyProtective effectBile secretionImmune pathwaysRevisiting 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
2013
Isolation and characterization of biliary epithelial and stromal cells from resected human cholangiocarcinoma: A novel in vitro model to study tumor-stroma interactions
MASSANI M, STECCA T, FABRIS L, CARATOZZOLO E, RUFFOLO C, FURLANETTO A, MORTON S, CADAMURO M, STRAZZABOSCO M, BASSI N. Isolation and characterization of biliary epithelial and stromal cells from resected human cholangiocarcinoma: A novel in vitro model to study tumor-stroma interactions. Oncology Reports 2013, 30: 1143-1148. PMID: 23807641, DOI: 10.3892/or.2013.2568.Peer-Reviewed Original ResearchMeSH KeywordsBile Duct NeoplasmsBile Ducts, IntrahepaticBiomarkers, TumorCell CommunicationCholangiocarcinomaCoculture TechniquesEpithelial-Mesenchymal TransitionFibroblastsFlow CytometryFluorescent Antibody TechniqueHumansImmunoenzyme TechniquesImmunomagnetic SeparationNeoplasm GradingStromal CellsTumor Cells, CulturedConceptsHuman biliary epithelial cellsTumor-stroma interactionsCancer-associated fibroblastsStromal cellsOrganotypic co-culture modelPrimary culturesTumor cell originMesenchymal cell markersBiliary epithelial cellsCCA cell linesRat cholangiocarcinomaCo-culture modelDevastating malignancySurgical resectionBile ductPresent studySurgical specimensDesmoplastic reactionCholangiocarcinomaCell originHuman cholangiocarcinomaCell markersFluorescent immunocytochemistryEpithelial cellsCK7
2012
Cyclic AMP/PKA‐dependent paradoxical activation of Raf/MEK/ERK signaling in polycystin‐2 defective mice treated with sorafenib
Spirli C, Morell CM, Locatelli L, Okolicsanyi S, Ferrero C, Kim AK, Fabris L, Fiorotto R, Strazzabosco M. Cyclic AMP/PKA‐dependent paradoxical activation of Raf/MEK/ERK signaling in polycystin‐2 defective mice treated with sorafenib. Hepatology 2012, 56: 2363-2374. PMID: 22653837, PMCID: PMC3460040, DOI: 10.1002/hep.25872.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Agents, HormonalBenzenesulfonatesBile DuctsCaspase 3Cell ProliferationCells, CulturedCyclic AMP-Dependent Protein KinasesCystsDrug Therapy, CombinationEpithelial CellsKi-67 AntigenLiver DiseasesMAP Kinase Signaling SystemMiceMice, KnockoutNiacinamideOctreotidePhenylurea CompoundsPhosphorylationProtein Kinase InhibitorsProto-Oncogene Proteins B-rafProto-Oncogene Proteins c-rafPyridinesSorafenibTRPP Cation ChannelsConceptsRaf-1Cell proliferationB-RafPhosphorylated ERKRaf kinase activitySignal-regulated kinase 1/2 pathwayRAF inhibitorsCyclic adenosine monophosphateRaf/MEK/ERKCyst growthDefective miceKinase 1/2 pathwayParadoxical activationCAMP/PKAMEK/ERKPolycystin-2Kinase AKinase activityWT cellsDependent activationERK1/2 phosphorylationInhibitor 14Epithelial cellsAdenosine monophosphateERK
2010
Cholangiocyte Biology as Relevant to Cystic Liver Diseases
Lecchi S, Fabris L, Spirli C, Cadamuro M, Fiorotto R, Strazzabosco M. Cholangiocyte Biology as Relevant to Cystic Liver Diseases. Clinical Gastroenterology 2010, 23-43. DOI: 10.1007/978-1-60327-524-8_2.ChaptersLiver cystsLiver diseaseSevere life-threatening complicationsIntrahepatic bile duct epitheliumComplex intercellular signalingCystic liver diseaseProgressive cyst growthLife-threatening complicationsEpithelial cellsBile duct epitheliumIntrahepatic biliary treePolycystic liver diseaseExcessive fluid secretionRenal tubule epitheliumRecessive formExtracellular matrix remodelingBiliary treeBiliary epitheliumCystic diseaseDuct epitheliumCyst expansionCyst growthAutocrine mechanismTubule epitheliumHereditary disorder
2008
Morphological and Functional Features of Hepatic Cyst Epithelium in Autosomal Dominant Polycystic Kidney Disease
Alvaro D, Onori P, Alpini G, Franchitto A, Jefferson DM, Torrice A, Cardinale V, Stefanelli F, Mancino MG, Strazzabosco M, Angelico M, Attili A, Gaudio E. Morphological and Functional Features of Hepatic Cyst Epithelium in Autosomal Dominant Polycystic Kidney Disease. American Journal Of Pathology 2008, 172: 321-332. PMID: 18202196, PMCID: PMC2312356, DOI: 10.2353/ajpath.2008.070293.Peer-Reviewed Original ResearchMeSH KeywordsAgedBlotting, WesternCell ProliferationCiliaCyst FluidCystsEpitheliumEstradiolFemaleFluorescent Antibody TechniqueHumansImmunohistochemistryInsulin-Like Growth Factor ILiver DiseasesMaleMicroscopy, Electron, ScanningMiddle AgedPolycystic Kidney DiseasesReceptor, IGF Type 1Receptors, EstrogenConceptsAdult autosomal dominant polycystic kidney diseaseInsulin-like growth factor-1Autosomal dominant polycystic kidney diseaseDominant polycystic kidney diseaseEstrogen receptorCyst epitheliumPolycystic kidney diseaseCyst fluidCell nuclear antigenKidney diseaseGrowth hormone receptorHormone receptorsNuclear antigenHepatic cyst fluidHuman cyst fluidEpithelial cellsRole of estrogenGrowth factor-1ADPKD patientsEstrogen antagonismImmunohistochemical expressionLarge cystsSmall cystsTherapeutic strategiesMTS proliferation
2001
Ductular morphogenesis and functional polarization of normal human biliary epithelial cells in three-dimensional culture
Ishida Y, Smith S, Wallace L, Sadamoto T, Okamoto M, Auth M, Strazzabosco M, Fabris L, Medina J, Prieto J, Strain A, Neuberger J, Joplin R. Ductular morphogenesis and functional polarization of normal human biliary epithelial cells in three-dimensional culture. Journal Of Hepatology 2001, 35: 2-9. PMID: 11495037, DOI: 10.1016/s0168-8278(01)00078-2.Peer-Reviewed Original ResearchConceptsCollagen gel cultureHuman biliary epithelial cellsEpithelial cellsGel cultureGrowth factorHuman hepatocyte growth factorThree-dimensional cultureBiliary epithelial cellsThree-dimensional aggregatesNormal human biliary epithelial cellsFoetal bovine serumMorphogenesisCell typesAnion exchanger 2Hepatocyte growth factorFunctional polarizationFunctional differentiationFunctional markersExchanger 2Monolayer culture systemCentral lumenPhenotypic markersCollagen gelsNumber of aggregatesCulture system