2023
Cell-matrix interactions control biliary organoid polarity, architecture, and differentiation
Fiorotto R, Mariotti V, Taleb S, Zehra S, Nguyen M, Amenduni M, Strazzabosco M. Cell-matrix interactions control biliary organoid polarity, architecture, and differentiation. Hepatology Communications 2023, 7: e0094. PMID: 36972396, PMCID: PMC10503667, DOI: 10.1097/hc9.0000000000000094.Peer-Reviewed Original ResearchConceptsBiliary organoidsNovel organoid modelImmune cell typesOrganotypic culture systemProinflammatory chemokinesStem cell featuresBiliary epitheliumExtracellular matrixEpithelial permeabilityImportant causeBile acidsBiliary differentiationBile transportHuman liverOrganoid modelsDisease modelsCholangiopathyCell featuresTight junctionsLiverCell typesInternal lumenOrganoidsSingle-cell transcriptomicsPathogenic bacteria
2020
The Emerging Role of Macrophages in Chronic Cholangiopathies Featuring Biliary Fibrosis: An Attractive Therapeutic Target for Orphan Diseases
Cadamuro M, Girardi N, Gores GJ, Strazzabosco M, Fabris L. The Emerging Role of Macrophages in Chronic Cholangiopathies Featuring Biliary Fibrosis: An Attractive Therapeutic Target for Orphan Diseases. Frontiers In Medicine 2020, 7: 115. PMID: 32373615, PMCID: PMC7186419, DOI: 10.3389/fmed.2020.00115.Peer-Reviewed Original ResearchBiliary fibrogenesisBiliary fibrosisChronic liver diseaseCongenital hepatic fibrosisEffective therapeutic approachHepatic stellate cellsPotential novel targetAttractive therapeutic targetMost cholangiopathiesChronic cholangiopathiesLiver diseasePortal fibroblastsHepatic fibrosisModern hepatologyLiver fibrosisBiliary epitheliumDisease progressionCell effectorsTherapeutic approachesCholangiopathyStellate cellsTherapeutic targetFibrosisOrphan diseaseNovel targetEffects of Cytokines and Nitric Oxide on Bicarbonate Secretion by Cholangiocytes
Spirlì C, Okolicsanyi L, Strazzabosco M. Effects of Cytokines and Nitric Oxide on Bicarbonate Secretion by Cholangiocytes. 2020, 81-88. DOI: 10.1201/9780367813888-7.Peer-Reviewed Original ResearchInflammatory mediatorsBiliary epitheliumRole of inflammationSecretory mechanismElectrolyte transportEffects of cytokinesPathophysiology of cholangiopathiesProgressive cholestasisFibrogenetic processInhibition of cAMPProliferative responseBicarbonate secretionPathogenetic sequenceCholestasisDuctal cholestasisCAMP formationCholangiopathyNitric oxideAvailable evidenceCell damageAdenylyl cyclaseCytokinesMediatorsCholangiocytesEpithelium
2019
The challenges of primary biliary cholangitis: What is new and what needs to be done
Terziroli Beretta-Piccoli B, Mieli-Vergani G, Vergani D, Vierling JM, Adams D, Alpini G, Banales JM, Beuers U, Björnsson E, Bowlus C, Carbone M, Chazouillères O, Dalekos G, De Gottardi A, Harada K, Hirschfield G, Invernizzi P, Jones D, Krawitt E, Lanzavecchia A, Lian ZX, Ma X, Manns M, Mavilio D, Quigley EM, Sallusto F, Shimoda S, Strazzabosco M, Swain M, Tanaka A, Trauner M, Tsuneyama K, Zigmond E, Gershwin ME. The challenges of primary biliary cholangitis: What is new and what needs to be done. Journal Of Autoimmunity 2019, 105: 102328. PMID: 31548157, DOI: 10.1016/j.jaut.2019.102328.Peer-Reviewed Original ResearchConceptsPrimary biliary cholangitisAnti-mitochondrial autoantibodiesBiochemical cholestasisBiliary cholangitisBiliary epitheliumUrsodeoxycholic acidPBC-specific anti-nuclear antibodiesBile acidsToxic hydrophobic bile acidsAutoimmune liver diseaseSecond-line treatmentFirst-line treatmentAnti-nuclear antibodiesReliable disease markersEarly disease stagesCholestatic biochemical profileNew therapeutic approachesHydrophobic bile acidsAutoimmune originSeronegative casesLiver histologyAutoimmune attackFemale preponderanceHistologic confirmationImmunologic pathways
2018
Animal models of cholestasis: An update on inflammatory cholangiopathies
Mariotti V, Cadamuro M, Spirli C, Fiorotto R, Strazzabosco M, Fabris L. Animal models of cholestasis: An update on inflammatory cholangiopathies. Biochimica Et Biophysica Acta (BBA) - Molecular Basis Of Disease 2018, 1865: 954-964. PMID: 30398152, DOI: 10.1016/j.bbadis.2018.07.025.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAnimal modelsPro-fibrotic signalsChronic liver diseasePrimary biliary cholangitisBile duct ligationFrequent clinical conditionBiliary injuryBiliary cholangitisBiliary obstructionLiver diseaseBiliary epitheliumDuct ligationInflammatory cholangiopathyAdaptive immunityClinical conditionsControversial diseasePathogenetic sequenceCholangiopathyCholestasisExperimental modelCholangitisDiseasePrimary targetChemical inductionCell elementsSrc kinase inhibition reduces inflammatory and cytoskeletal changes in ΔF508 human cholangiocytes and improves cystic fibrosis transmembrane conductance regulator correctors efficacy
Fiorotto R, Amenduni M, Mariotti V, Fabris L, Spirli C, Strazzabosco M. Src kinase inhibition reduces inflammatory and cytoskeletal changes in ΔF508 human cholangiocytes and improves cystic fibrosis transmembrane conductance regulator correctors efficacy. Hepatology 2018, 67: 972-988. PMID: 28836688, PMCID: PMC5783790, DOI: 10.1002/hep.29400.Peer-Reviewed Original ResearchMeSH KeywordsAminophenolsAminopyridinesAnimalsBenzodioxolesBiliary TractCell Culture TechniquesChloride Channel AgonistsCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorCytokinesCytoskeletonEpithelial CellsFluorescent Antibody TechniqueHumansInduced Pluripotent Stem CellsInflammationMiceMicroscopy, ConfocalPyrimidinesQuinolonesSignal TransductionSrc-Family KinasesConceptsBiliary epitheliumCystic fibrosisToll-like receptor 4Cystic fibrosis transmembrane conductance regulatorFluid secretionActivated B cells (NF-κB) activationClinical liver diseaseStrong translational potentialCause of deathB cell activationSrc kinase inhibitionFibrosis transmembrane conductance regulatorTransmembrane conductance regulatorInflammatory changesPharmacological therapyProinflammatory changesProinflammatory chemokinesInflammation contributesLiver diseaseHuman cholangiopathiesReceptor 4Healthy controlsLiver patientsCF patientsVX-770
2017
Molecular Mechanisms Driving Cholangiocarcinoma Invasiveness: An Overview
Brivio S, Cadamuro M, Fabris L, Strazzabosco M. Molecular Mechanisms Driving Cholangiocarcinoma Invasiveness: An Overview. Gene Expression 2017, 18: 31-50. PMID: 29070148, PMCID: PMC5860940, DOI: 10.3727/105221617x15088670121925.Peer-Reviewed Original ResearchConceptsMajority of patientsPrimary liver cancerCancer-related deathPotential prognostic relevanceDevelopment of metastasesPro-oncogenic pathwaysNovel druggable targetsMechanism of actionCholangiocarcinoma invasivenessMesenchymal-like phenotypeDevastating malignancyCurative treatmentMolecular mechanismsPoor prognosisPrognostic relevancePrimary tumorBiliary epitheliumLiver cancerUseful biomarkerAbnormal activationCCA cell invasionMost carcinomasCCA cellsTumor microenvironmentCholangiocarcinomaPathophysiologic implications of innate immunity and autoinflammation in the biliary epithelium
Strazzabosco M, Fiorotto R, Cadamuro M, Spirli C, Mariotti V, Kaffe E, Scirpo R, Fabris L. Pathophysiologic implications of innate immunity and autoinflammation in the biliary epithelium. Biochimica Et Biophysica Acta (BBA) - Molecular Basis Of Disease 2017, 1864: 1374-1379. PMID: 28754453, PMCID: PMC5785585, DOI: 10.1016/j.bbadis.2017.07.023.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsToll-like receptorsLiver damageCystic fibrosis-related liver diseaseInnate immunityDamage-associated molecular patternsEpithelial innate immunityPro-inflammatory behaviorBiliary epithelial cellsNumber of receptorsJesus BanalesMarco MarzioniNicholas LaRussoPeter JansenLiver injuryLiver diseaseBile flowInflammatory processBiliary epitheliumInflammatory responsePathophysiologic implicationsReparative processesNumber of evidencesFirst defense lineCholangiocytesMolecular patternsEmerging concepts in biliary repair and fibrosis
Fabris L, Spirli C, Cadamuro M, Fiorotto R, Strazzabosco M. Emerging concepts in biliary repair and fibrosis. AJP Gastrointestinal And Liver Physiology 2017, 313: g102-g116. PMID: 28526690, PMCID: PMC5582882, DOI: 10.1152/ajpgi.00452.2016.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsReactive ductular cellsBiliary repairBiliary treeDuctular cellsProliferation of cholangiocytesCongenital hepatic fibrosisBiliary fibrosisInflammatory changesBiliary atresiaChronic cholangiopathiesClinical progressionClinical hepatologyHepatic fibrosisLiver repairMajor unmetBiliary epitheliumChronic diseasesChronic damageReparative responseAlagille syndromeLiver pathophysiologyReparative processesFibrosisPathological repairCellular elements
2016
Macrophage recruitment by fibrocystin‐defective biliary epithelial cells promotes portal fibrosis in congenital hepatic fibrosis
Locatelli L, Cadamuro M, Spirlì C, Fiorotto R, Lecchi S, Morell C, Popov Y, Scirpo R, De Matteis M, Amenduni M, Pietrobattista A, Torre G, Schuppan D, Fabris L, Strazzabosco M. Macrophage recruitment by fibrocystin‐defective biliary epithelial cells promotes portal fibrosis in congenital hepatic fibrosis. Hepatology 2016, 63: 965-982. PMID: 26645994, PMCID: PMC4764460, DOI: 10.1002/hep.28382.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, NeoplasmChemokinesClodronic AcidCollagenDisease Models, AnimalEpithelial CellsGenetic Diseases, InbornIntegrinsLiver CirrhosisMacrophagesMiceMyofibroblastsReceptors, Cell SurfaceSnail Family Transcription FactorsTranscription FactorsTransforming Growth Factor beta1Tumor Necrosis Factor-alphaConceptsCongenital hepatic fibrosisMacrophage recruitmentPortal hypertensionPortal fibrosisHepatic fibrosisLiver fibrosisCell dysfunctionBile duct changesRange of chemokinesLow-grade inflammationProgressive liver fibrosisDuctal plate malformationEpithelial cell dysfunctionGrowth factor-β1Biliary epithelial cellsBiliary fibrosisLiver failureMacrophage infiltratesLiver cystsDuct changesProinflammatory cytokinesPeribiliary fibrosisBiliary epitheliumDisease progressionM1 phenotype
2015
Oxidative Stress in Nonautoimmune Biliary Diseases
Cadamuro M, Fabris L, Strazzabosco M. Oxidative Stress in Nonautoimmune Biliary Diseases. Oxidative Stress In Applied Basic Research And Clinical Practice 2015, 309-324. DOI: 10.1007/978-3-319-15539-5_13.Peer-Reviewed Original Research
2012
Polycystic liver diseases
Fabris L, McCrann C, Strazzabosco M. Polycystic liver diseases. 2012, 713-718. DOI: 10.1002/9781118321386.ch96.ChaptersPolycystic liver diseaseLiver diseaseCongenital hepatic fibrosisAutosomal dominant polycystic liver diseaseDifferent clinical entitiesChronic complicationsKidney involvementLiver transplantationPortal hypertensionCaroli's diseaseMedical therapyClinical entityLiver functionMultiple cystsSurgical approachHepatic fibrosisBiliary epitheliumHepatic parenchymaLiver parenchymaProgressive enlargementInterventional radiologyDiseaseGenetic defectsEndoplasmic reticulum-associated proteinParenchyma
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 acidPolycystic Liver Diseases: Congenital Disorders of Cholangiocyte Signaling
Strazzabosco M, Somlo S. Polycystic Liver Diseases: Congenital Disorders of Cholangiocyte Signaling. Gastroenterology 2011, 140: 1855-1859.e1. PMID: 21515270, PMCID: PMC3109236, DOI: 10.1053/j.gastro.2011.04.030.Peer-Reviewed Original ResearchConceptsPolycystic liver diseaseLiver cyst formationClinical featuresLiver diseaseMultiple cystsDisease progressionBiliary epitheliumLiver parenchymaProgressive enlargementCongenital diseaseCyst formationCholangiocyte physiologyCongenital disorderPotential targetGenetic defectsDiseaseProgressionDisordersInheritance patternSignalingIntracellular organellesDifferent entitiesTherapyKidneyPathwayEpithelial–Mesenchymal Interactions in Biliary Diseases
Fabris L, Strazzabosco M. Epithelial–Mesenchymal Interactions in Biliary Diseases. Seminars In Liver Disease 2011, 31: 011-032. PMID: 21344348, PMCID: PMC3729030, DOI: 10.1055/s-0031-1272832.Peer-Reviewed Original ResearchConceptsReactive cholangiocytesChemo/cytokinesBile secretory functionLiver repair mechanismsDe novo expressionDifferent mesenchymal cell typesMost cholangiopathiesCell typesPortal fibrosisPortal infiltratesLiver diseaseBiliary diseaseUnderlying molecular mechanismsBiliary epitheliumDifferent etiologiesLiver repairSecretory functionNovo expressionCholangiopathyBiliary cellsCentral mechanismsMesenchymal cell typesMesenchymal propertiesEndothelial cellsGrowth factor
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
Functional Anatomy of Normal Bile Ducts
Strazzabosco M, Fabris L. Functional Anatomy of Normal Bile Ducts. The Anatomical Record 2008, 291: 653-660. PMID: 18484611, PMCID: PMC3743051, DOI: 10.1002/ar.20664.Peer-Reviewed Original ResearchConceptsBile ductBiliary treeExtrahepatic bile ductSmall bile ductsNormal bile ductsLiver progenitor cellsBile productionBiliary epitheliumMajor ductsSecretory functionVascular structuresProgenitor cellsCholangiocyte functionFunctional anatomyBileDuctCholangiocytesIntestineFunctional interactionMorphological heterogeneityNerveGallbladderVariety of functionsEpithelium
2001
Proinflammatory Cytokines Inhibit Secretion in Rat Bile Duct Epithelium
Spirlı̀ C, Nathanson M, Fiorotto R, Duner E, Denson L, Sanz J, Di Virgilio F, Okolicsanyi L, Casagrande F, Strazzabosco M. Proinflammatory Cytokines Inhibit Secretion in Rat Bile Duct Epithelium. Gastroenterology 2001, 121: 156-169. PMID: 11438505, DOI: 10.1053/gast.2001.25516.Peer-Reviewed Original ResearchConceptsProinflammatory cytokinesFluorescein-labeled dextranIL-1Interferon gammaCAMP-dependent fluid secretionCystic fibrosis transmembrane conductance regulatorBile duct epitheliumRat bile duct epitheliaTumor necrosis factorCyclic adenosine monophosphate levelsSecretin receptorAdenosine monophosphate levelsBile duct unitsDuctular cholestasisPortal inflammationCholestatic disordersIL-6Inflammatory cytokinesTNF-alphaBiliary epitheliumNecrosis factorCellular cyclic adenosine monophosphate (cAMP) levelsDuct epitheliumPurinergic agonistsSR expression
2000
Pathophysiology of the intrahepatic biliary epithelium
Strazzabosco M, Spirlì C, Okolicsanyi L. Pathophysiology of the intrahepatic biliary epithelium. Journal Of Gastroenterology And Hepatology 2000, 15: 244-253. PMID: 10764023, DOI: 10.1046/j.1440-1746.2000.02091.x.Peer-Reviewed Original ResearchConceptsIntrahepatic biliary epitheliumBiliary epitheliumIntrahepatic bile duct epitheliumChronic cholestatic disorderBile duct epitheliumCholangiocyte functionBasic disease mechanismsPortal inflammationBiliary atresiaGastrointestinal hormonesCholestatic disordersPathophysiological pointBiliary treeCholangiocyte pathophysiologyImmune regulationPharmacological approachesNormal epitheliumCholangiocyte proliferationCholangiopathyDuct epitheliumInfectious agentsImportant causeBile acidsCystic fibrosisImmunoglobulin A.
1997
Transport systems in cholangiocytes: their role in bile formation and cholestasis.
Strazzabosco M. Transport systems in cholangiocytes: their role in bile formation and cholestasis. The Yale Journal Of Biology And Medicine 1997, 70: 427-34. PMID: 9626763, PMCID: PMC2589334.Peer-Reviewed Original ResearchConceptsBiliary epitheliumCa-activated Cl channelsChronic cholestatic disorderPathogenesis of cholestasisBile duct diseaseCholangiocyte deathFormation of bilePortal inflammationBiliary cirrhosisProinflammatory mediatorsLiver diseaseClinical picturePathophysiological pointCholestatic disordersDuct diseaseProliferative responseBiliary constituentsBile acidsCystic fibrosisPortal spacesSecretory functionBile formationCholestasisDuctular secretionSecretory activity