2024
396 Introduction of CFTR mutations in isogenic induced pluripotent stem cell–derived cholangiocytes and three-dimensional organoids provides pathophysiological information relevant for treatment of CF-related liver disease
Taleb S, Zaman S, Strazzabosco M, Fiorotto R. 396 Introduction of CFTR mutations in isogenic induced pluripotent stem cell–derived cholangiocytes and three-dimensional organoids provides pathophysiological information relevant for treatment of CF-related liver disease. Journal Of Cystic Fibrosis 2024, 23: s208. DOI: 10.1016/s1569-1993(24)01236-0.Peer-Reviewed Original ResearchFRI-162 Analysis of cellular crosstalk in fibrocystic liver disease (PKHD1-/-mouse) reveals a central role for cholangiocytes, neutrophils and chronic biliary infection in disease pathogenesis
Syeda Z, Bauer-Pisani T, Taleb S, Fiorotto R, Strazzabosco M. FRI-162 Analysis of cellular crosstalk in fibrocystic liver disease (PKHD1-/-mouse) reveals a central role for cholangiocytes, neutrophils and chronic biliary infection in disease pathogenesis. Journal Of Hepatology 2024, 80: s697. DOI: 10.1016/s0168-8278(24)01983-4.Peer-Reviewed Original ResearchFRI-155 Introduction of class I-III mutations of CFTR in isogenic human iPSCs-derived cholangiocytes and 3D organoids provides pathophysiological information relevant for treatment of cystic fibrosis-related liver disease (CFLD)
Taleb S, Zaman S, Syeda Z, Strazzabosco M, Fiorotto R. FRI-155 Introduction of class I-III mutations of CFTR in isogenic human iPSCs-derived cholangiocytes and 3D organoids provides pathophysiological information relevant for treatment of cystic fibrosis-related liver disease (CFLD). Journal Of Hepatology 2024, 80: s695. DOI: 10.1016/s0168-8278(24)01978-0.Peer-Reviewed Original ResearchProminent role of gut dysbiosis in the pathogenesis of cystic fibrosis-related liver disease in mice
Bertolini A, Nguyen M, Zehra S, Taleb S, Bauer-Pisani T, Palm N, Strazzabosco M, Fiorotto R. Prominent role of gut dysbiosis in the pathogenesis of cystic fibrosis-related liver disease in mice. Journal Of Hepatology 2024, 81: 429-440. PMID: 38554847, PMCID: PMC11347101, DOI: 10.1016/j.jhep.2024.03.041.Peer-Reviewed Original ResearchCystic fibrosis-related liver diseaseCystic fibrosis transmembrane conductance regulatorCFTR-KO miceDefective cystic fibrosis transmembrane conductance regulatorCFTR-KOIntestinal permeabilityLiver diseaseGut-liver axisGut dysbiosisIncreased morbidityMortality of CF patientsAssociated with increased intestinal permeabilityLiver pathologyDevelopment of cholangiopathyCftr-knockout miceTransmembrane conductance regulatorIncreased intestinal permeabilityTargeted therapeutic strategiesFecal microbiota transferAttenuates liver diseaseExcessive inflammatory responseFITC-dextran assayPresence of neutrophilsActivation of pro-inflammatoryCFTR-knockout
2022
Bile acids and their receptors: modulators and therapeutic targets in liver inflammation
Bertolini A, Fiorotto R, Strazzabosco M. Bile acids and their receptors: modulators and therapeutic targets in liver inflammation. Seminars In Immunopathology 2022, 44: 547-564. PMID: 35415765, PMCID: PMC9256560, DOI: 10.1007/s00281-022-00935-7.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsBile acidsLiver diseaseTherapeutic targetAutoimmune liver diseaseCholestatic liver diseaseBile acid receptorAbsorption of lipidsFat-soluble vitaminsLiver inflammationInflammatory diseasesImmunomodulatory propertiesAcid receptorsInflammationDiseaseReceptorsClinical applicationLiverNutrient metabolismPathway
2021
Novel approaches to liver disease diagnosis and modeling
Oliveira AG, Fiorotto R. Novel approaches to liver disease diagnosis and modeling. Translational Gastroenterology And Hepatology 2021, 6: 19-19. PMID: 33824923, PMCID: PMC7829068, DOI: 10.21037/tgh-20-109.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
2020
Recent Advances in Practical Methods for Liver Cell Biology: A Short Overview
Torres S, Abdullah Z, Brol MJ, Hellerbrand C, Fernandez M, Fiorotto R, Klein S, Königshofer P, Liedtke C, Lotersztajn S, Nevzorova YA, Schierwagen R, Reiberger T, Uschner FE, Tacke F, Weiskirchen R, Trebicka J. Recent Advances in Practical Methods for Liver Cell Biology: A Short Overview. International Journal Of Molecular Sciences 2020, 21: 2027. PMID: 32188134, PMCID: PMC7139397, DOI: 10.3390/ijms21062027.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsLiver cell biologyCell biologyLiver diseaseHepatocellular carcinomaHigh-throughput assaysNon-parenchymal liver cellsSophisticated animal modelsPortal hypertensionLiver pathologyCell isolation techniquesTherapeutic strategiesAnimal modelsStem cellsBiologyPreclinical testingVivo assessmentLiver cellsOrganoid researchVivo methodsNovel opportunitiesDiseaseResearch modalitiesCellsRecent advancesHypertension
2019
Pathobiology of inherited biliary diseases: a roadmap to understand acquired liver diseases
Fabris L, Fiorotto R, Spirli C, Cadamuro M, Mariotti V, Perugorria MJ, Banales JM, Strazzabosco M. Pathobiology of inherited biliary diseases: a roadmap to understand acquired liver diseases. Nature Reviews Gastroenterology & Hepatology 2019, 16: 497-511. PMID: 31165788, PMCID: PMC6661007, DOI: 10.1038/s41575-019-0156-4.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCystic fibrosis-related liver diseaseFibropolycystic liver diseaseLiver diseasePolycystic liver diseaseBiliary repairAlagille syndromeEpithelial toll-like receptor 4Toll-like receptor 4Acquired liver diseasesGut-derived productsPrimary sclerosing cholangitisDuct epithelial cellsSclerosing cholangitisΒ-catenin signalingPortal fibrosisBiliary diseaseIL-1βUnknown etiologyDependent cytokinesReceptor 4Peribiliary inflammationRole of NotchCholangiopathyNovel treatmentsCyst growthPathophysiology of Cystic Fibrosis Liver Disease: A Channelopathy Leading to Alterations in Innate Immunity and in Microbiota
Fiorotto R, Strazzabosco M. Pathophysiology of Cystic Fibrosis Liver Disease: A Channelopathy Leading to Alterations in Innate Immunity and in Microbiota. Cellular And Molecular Gastroenterology And Hepatology 2019, 8: 197-207. PMID: 31075352, PMCID: PMC6664222, DOI: 10.1016/j.jcmgh.2019.04.013.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCF-associated liver diseaseLiver diseaseCystic fibrosisInnate immunityCystic fibrosis liver diseaseEpithelial innate immunityCystic fibrosis transmembrane conductance regulatorFibrosis transmembrane conductance regulatorNonpulmonary causesCF adultsTransmembrane conductance regulatorLiver complicationsMutations of CFTRPediatric populationAltered microbiotaIntestinal diseaseBile secretionCF mortalityDiseaseNew drugsConductance regulatorPotential targetLife expectancyBasic defectPathophysiology
2018
Liver diseases in the dish: iPSC and organoids as a new approach to modeling liver diseases
Fiorotto R, Amenduni M, Mariotti V, Fabris L, Spirli C, Strazzabosco M. Liver diseases in the dish: iPSC and organoids as a new approach to modeling liver diseases. Biochimica Et Biophysica Acta (BBA) - Molecular Basis Of Disease 2018, 1865: 920-928. PMID: 30264693, PMCID: PMC6658095, DOI: 10.1016/j.bbadis.2018.08.038.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsLiver diseaseStem cell fieldHepatocyte-like cellsPluripotent stem cellsRegenerative medicineNext-generation toolsSurvival of patientsRecent technological advancesMononuclear blood cellsPotential applicationsGene editingQuality of lifeLiver cell typesDisease modelingCell fieldAdequate cellular modelsLiver transplantationOrgan failureLiver specimensDiseaseStem cellsBlood cellsLiver cellsDrug testingSkin fibroblastsAnimal 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 elementsAnimal models for cystic fibrosis liver disease (CFLD)
Fiorotto R, Amenduni M, Mariotti V, Cadamuro M, Fabris L, Spirli C, Strazzabosco M. Animal models for cystic fibrosis liver disease (CFLD). Biochimica Et Biophysica Acta (BBA) - Molecular Basis Of Disease 2018, 1865: 965-969. PMID: 30071276, PMCID: PMC6474816, DOI: 10.1016/j.bbadis.2018.07.026.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCystic fibrosis liver diseaseLiver diseaseAnimal modelsCF animal modelsCystic fibrosisEpithelial innate immunityMore specific treatmentsNovel therapeutic treatmentsDifferent animal modelsLiver manifestationsSevere complicationsPathogenetic factorSpecific treatmentCF miceGut microbiotaInnate immunityTherapeutic treatmentLiver phenotypeDiseaseChloride channelsCystic fibrosis transmembrane conductance regulator (CFTR) channelCFTR expressionHuman diseasesTreatmentApical membraneSrc 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
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-TBGPathophysiologic 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 patterns
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 pathwaysAdenylyl cyclase 5 links changes in calcium homeostasis to cAMP-dependent cyst growth in polycystic liver disease
Spirli C, Mariotti V, Villani A, Fabris L, Fiorotto R, Strazzabosco M. Adenylyl cyclase 5 links changes in calcium homeostasis to cAMP-dependent cyst growth in polycystic liver disease. Journal Of Hepatology 2016, 66: 571-580. PMID: 27826057, PMCID: PMC5316496, DOI: 10.1016/j.jhep.2016.10.032.Peer-Reviewed Original ResearchMeSH KeywordsAdenylyl Cyclase InhibitorsAdenylyl CyclasesAnimalsCalciumCell ProliferationCyclic AMPCystsDisease Models, AnimalHomeostasisHumansLiver DiseasesMAP Kinase Signaling SystemMiceMice, KnockoutPolycystic Kidney, Autosomal DominantRNA InterferenceSignal TransductionStromal Interaction Molecule 1TRPP Cation ChannelsVascular Endothelial Growth Factor AConceptsProgressive cyst growthPolycystic liver diseaseNovel therapeutic targetLiver diseaseKO miceCyst growthTherapeutic targetBiliary organoidsDouble conditional knockout miceCAMP productionAutosomal dominant polycystic kidney diseaseVascular endothelial growth factorCell proliferationDominant polycystic kidney diseaseEndothelial growth factorConditional knockout micePolycystic kidney diseaseLiver transplantationLevels of cAMPStore-operated CaCystic areasKidney diseaseCyst sizeVivo treatmentKnockout miceCystic Fibrosis–Related Liver Diseases: New Paradigm for Treatment Based on Pathophysiology
Fiorotto R, Strazzabosco M. Cystic Fibrosis–Related Liver Diseases: New Paradigm for Treatment Based on Pathophysiology. Clinical Liver Disease 2016, 8: 113-116. PMID: 31041076, PMCID: PMC6490209, DOI: 10.1002/cld.583.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsLiver diseaseCystic fibrosis
2015
Stimulation of nuclear receptor peroxisome proliferator–activated receptor‐γ limits NF‐κB‐dependent inflammation in mouse cystic fibrosis biliary epithelium
Scirpo R, Fiorotto R, Villani A, Amenduni M, Spirli C, Strazzabosco M. Stimulation of nuclear receptor peroxisome proliferator–activated receptor‐γ limits NF‐κB‐dependent inflammation in mouse cystic fibrosis biliary epithelium. Hepatology 2015, 62: 1551-1562. PMID: 26199136, PMCID: PMC4618241, DOI: 10.1002/hep.28000.Peer-Reviewed Original ResearchConceptsCystic fibrosis-associated liver diseaseNF-κB-dependent inflammationCFTR knockout miceLiver diseaseToll-like receptor-4/nuclear factor kappaB-cells inhibitor alphaCystic fibrosis transmembrane conductance regulator knockout miceKappa light polypeptide gene enhancerPeroxisome proliferator-activated receptorStimulation of PPARDextran sodium sulfateAnti-inflammatory effectsChronic inflammatory stateLight polypeptide gene enhancerNuclear receptorsNuclear factor kappaProliferator-activated receptorDependent immune mechanismQuality of lifeActivated B cellsCystic fibrosis patientsChronic cholangiopathiesInflammatory stateProinflammatory cytokinesPortal endotoxemia
2013
Notch 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 Transduction