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
2007
Combined Double Lung–Liver Transplantation for Cystic Fibrosis Without Cardio‐Pulmonary By‐Pass
Corno V, Dezza M, Lucianetti A, Codazzi D, Carrara B, Pinelli D, Parigi P, Guizzetti M, Strazzabosco M, Melzi M, Gaffuri G, Sonzogni V, Rossi A, Fagiuoli S, Colledan M. Combined Double Lung–Liver Transplantation for Cystic Fibrosis Without Cardio‐Pulmonary By‐Pass. American Journal Of Transplantation 2007, 7: 2433-2438. PMID: 17845577, DOI: 10.1111/j.1600-6143.2007.01945.x.Peer-Reviewed Original ResearchConceptsLung-liver transplantationCystic fibrosisExtended right graftsSitu split liversWhole liver graftsEnd-stage lungUse of CPBRight graftSplit liverLung transplantPortal hypertensionRespiratory failureLiver graftsLiver diseaseTherapeutic optionsStage lungTransplantationEffective procedureYoung menPatientsFibrosisGraftRecipientsCPBBasiliximab
2000
Ca2+‐activated Cl− channels can substitute for CFTR in stimulation of pancreatic duct bicarbonate secretion
ZSEMBERY Á, Strazzabosco M, Graf J. Ca2+‐activated Cl− channels can substitute for CFTR in stimulation of pancreatic duct bicarbonate secretion. The FASEB Journal 2000, 14: 2345-2356. PMID: 11053257, DOI: 10.1096/fj.99-0509com.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateBicarbonatesCalciumCesiumChloride ChannelsChloridesCyclic AMPCystic Fibrosis Transmembrane Conductance RegulatorGlyburideGlycerolHumansHydrogen-Ion ConcentrationMembrane PotentialsMutationPancreatic DuctsPatch-Clamp TechniquesPotassium ChannelsTumor Cells, CulturedPathophysiology 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.
1998
Liver and Biliary Problems in Cystic Fibrosis
Colombo C, Battezzati P, Strazzabosco M, Podda M. Liver and Biliary Problems in Cystic Fibrosis. Seminars In Liver Disease 1998, 18: 227-235. PMID: 9773423, DOI: 10.1055/s-2007-1007159.Peer-Reviewed Original ResearchConceptsCF-associated liver diseaseLiver diseaseCF patientsCystic fibrosisEarly-stage liver diseaseEssential fatty acid statusExtra-hepatic causesBile duct damageStage liver diseaseBile acid therapyHepatic excretory functionBile acid compositionFatty acid statusUseful therapeutic approachImpaired secretory functionQuality of lifeSpecific CFTR mutationsCholangiocyte pathobiologyHepatic assessmentLiver biochemistryCumulative incidenceDuct damageLiver histologyBiliary problemsMajor complications
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