2019
Pathophysiology 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
Animal 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
2016
Cystic 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
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
2005
Glibenclamide Stimulates Fluid Secretion in Rodent Cholangiocytes Through a Cystic Fibrosis Transmembrane Conductance Regulator-Independent Mechanism
Spirlì C, Fiorotto R, Song L, Santos-Sacchi J, Okolicsanyi L, Masier S, Rocchi L, Vairetti MP, de Bernard M, Melero S, Pozzan T, Strazzabosco M. Glibenclamide Stimulates Fluid Secretion in Rodent Cholangiocytes Through a Cystic Fibrosis Transmembrane Conductance Regulator-Independent Mechanism. Gastroenterology 2005, 129: 220-233. PMID: 16012949, DOI: 10.1053/j.gastro.2005.03.048.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsATP-Binding Cassette TransportersBile DuctsBody FluidsCalciumCell LineCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorElectric CapacitanceElectric ConductivityGlyburideHypoglycemic AgentsLiverMiceMice, Inbred CFTRPatch-Clamp TechniquesPotassium ChannelsPotassium Channels, Inwardly RectifyingRatsReceptors, DrugSulfonylurea ReceptorsConceptsCystic fibrosisBiliary ductsCholangiocyte secretionFluid secretionAbility of glibenclamideCystic fibrosis transmembrane conductance regulatorIntracellular Ca 2Liver impairmentSevere complicationsLiver diseaseCholestatic diseaseRodent cholangiocytesGlibenclamideInhibitors of exocytosisAbstractTextFibrosisSecretionSecretory mechanismDiseaseMiceCholangiocytesRat cholangiocytesCFTR inhibitor