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
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
Pathophysiologic 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
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
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
2003
Cytokine-stimulated nitric oxide production inhibits adenylyl cyclase and cAMP-dependent secretion in cholangiocytes
Spirlì C, Fabris L, Duner E, Fiorotto R, Ballardini G, Roskams T, Larusso NF, Sonzogni A, Okolicsanyi L, Strazzabosco M. Cytokine-stimulated nitric oxide production inhibits adenylyl cyclase and cAMP-dependent secretion in cholangiocytes. Gastroenterology 2003, 124: 737-753. PMID: 12612912, DOI: 10.1053/gast.2003.50100.Peer-Reviewed Original ResearchMeSH KeywordsAdenylyl Cyclase InhibitorsAdenylyl CyclasesAnimalsBile DuctsBile Ducts, IntrahepaticCell LineCyclic AMPDrug SynergismGene ExpressionHumansInterferon-gammaIntracellular FluidIon TransportLiver DiseasesNitratesNitric OxideNitric Oxide DonorsNitric Oxide SynthaseNitric Oxide Synthase Type IINitritesRatsTumor Necrosis Factor-alphaConceptsPrimary sclerosing cholangitisProinflammatory cytokinesBiliary epitheliumAdenylyl cyclaseHuman chronic liver diseaseInducible nitric oxide synthaseChronic liver diseaseSecretory mechanismInhibition of ACNitric oxide synthaseTumor necrosis factorDependent fluid secretionReactive nitrogen oxide speciesCAMP-dependent secretionNOS-2 inhibitorCystic fibrosis transmembrane conductance regulatorCAMP-dependent ClDuctular cholestasisProgressive cholestasisSclerosing cholangitisLiver diseaseCholestatic effectLiver damageBile productionNOS2 induction
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