2018
β‐Catenin and interleukin‐1β–dependent chemokine (C‐X‐C motif) ligand 10 production drives progression of disease in a mouse model of congenital hepatic fibrosis
Kaffe E, Fiorotto R, Pellegrino F, Mariotti V, Amenduni M, Cadamuro M, Fabris L, Strazzabosco M, Spirli C. β‐Catenin and interleukin‐1β–dependent chemokine (C‐X‐C motif) ligand 10 production drives progression of disease in a mouse model of congenital hepatic fibrosis. Hepatology 2018, 67: 1903-1919. PMID: 29140564, PMCID: PMC5906178, DOI: 10.1002/hep.29652.Peer-Reviewed Original ResearchConceptsSignal transducerΒ-cateninJanus kinase/signal transducerKinase/signal transducerActivator of transcriptionProtein kinase ATranscription 3 (STAT3) phosphorylationHepatic disease 1 (PKHD1) geneNOD-like receptorsKinase ATranscription 3Novel therapeutic avenuesGenetic diseasesNuclear translocationCognate receptorsFamily 3Nuclear factorMouse modelPKHD1Activated B cellsPhosphorylationActivatorCyst growthTherapeutic avenuesAMG 487Src 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
The deleterious interplay between tumor epithelia and stroma in cholangiocarcinoma
Cadamuro M, Stecca T, Brivio S, Mariotti V, Fiorotto R, Spirli C, Strazzabosco M, Fabris L. The deleterious interplay between tumor epithelia and stroma in cholangiocarcinoma. Biochimica Et Biophysica Acta (BBA) - Molecular Basis Of Disease 2017, 1864: 1435-1443. PMID: 28757170, PMCID: PMC6386155, DOI: 10.1016/j.bbadis.2017.07.028.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsTumor reactive stromaReactive stromaMain cellular componentsDeleterious interplayCyto/chemokinesCellular componentsParacrine signalsPrognosis of cholangiocarcinomaTumor epithelial cellsCell interactionsEarly invasivenessJesus BanalesMarco MarzioniNicholas LaRussoPeter JansenDifferent cell elementsEpithelial cellsEpithelial malignanciesTumor behaviorTumor epitheliumGrowth factorNeoplastic cellsTumor progressionCentral roleStromal componentsPathophysiologic 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
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
2012
Cyclic AMP/PKA‐dependent paradoxical activation of Raf/MEK/ERK signaling in polycystin‐2 defective mice treated with sorafenib
Spirli C, Morell CM, Locatelli L, Okolicsanyi S, Ferrero C, Kim AK, Fabris L, Fiorotto R, Strazzabosco M. Cyclic AMP/PKA‐dependent paradoxical activation of Raf/MEK/ERK signaling in polycystin‐2 defective mice treated with sorafenib. Hepatology 2012, 56: 2363-2374. PMID: 22653837, PMCID: PMC3460040, DOI: 10.1002/hep.25872.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Agents, HormonalBenzenesulfonatesBile DuctsCaspase 3Cell ProliferationCells, CulturedCyclic AMP-Dependent Protein KinasesCystsDrug Therapy, CombinationEpithelial CellsKi-67 AntigenLiver DiseasesMAP Kinase Signaling SystemMiceMice, KnockoutNiacinamideOctreotidePhenylurea CompoundsPhosphorylationProtein Kinase InhibitorsProto-Oncogene Proteins B-rafProto-Oncogene Proteins c-rafPyridinesSorafenibTRPP Cation ChannelsConceptsRaf-1Cell proliferationB-RafPhosphorylated ERKRaf kinase activitySignal-regulated kinase 1/2 pathwayRAF inhibitorsCyclic adenosine monophosphateRaf/MEK/ERKCyst growthDefective miceKinase 1/2 pathwayParadoxical activationCAMP/PKAMEK/ERKPolycystin-2Kinase AKinase activityWT cellsDependent activationERK1/2 phosphorylationInhibitor 14Epithelial cellsAdenosine monophosphateERK
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
2009
Diferentially expressed adenylyl cyclase isoforms mediate secretory functions in cholangiocyte subpopulation
Strazzabosco M, Fiorotto R, Melero S, Glaser S, Francis H, Spirli C, Alpini G. Diferentially expressed adenylyl cyclase isoforms mediate secretory functions in cholangiocyte subpopulation. Hepatology 2009, 50: 244-252. PMID: 19444869, PMCID: PMC2738985, DOI: 10.1002/hep.22926.Peer-Reviewed Original ResearchMeSH KeywordsAdenylyl CyclasesAnimalsBile DuctsEpithelial CellsGene Expression RegulationIsoenzymesMaleRatsRats, Sprague-DawleyConceptsSoluble adenylyl cyclaseAdenylyl cyclasesGene expressionAC isoformsCyclic adenosine monophosphateAC gene expressionDifferent tissue specificitiesGroup of enzymesAdenylyl cyclase isoformsTissue specificityCholangiocyte secretionCyclase isoformsIsoformsSAC inhibitorIsohydric changesAdenylyl cyclaseIsoform expressionSACS geneReal-time polymerase chain reactionGenesAdenosine monophosphateAC8ExpressionCAMP levelsCAMP production
2007
Epithelial expression of angiogenic growth factors modulate arterial vasculogenesis in human liver development
Fabris L, Cadamuro M, Libbrecht L, Raynaud P, Spirlì C, Fiorotto R, Okolicsanyi L, Lemaigre F, Strazzabosco M, Roskams T. Epithelial expression of angiogenic growth factors modulate arterial vasculogenesis in human liver development. Hepatology 2007, 47: 719-728. PMID: 18157837, DOI: 10.1002/hep.22015.Peer-Reviewed Original ResearchConceptsVascular endothelial growth factorHepatic arteryAngiogenic growth factorsBile ductAngiopoietin-1Tie-2Growth factorAngiopoietin-2VEGFR-1Endothelial cellsMural cellsCognate receptorsIntrahepatic bile ductsClose anatomical relationshipFetal human liverDifferent gestational agesEndothelial growth factorDifferent maturational stagesGestational ageHuman liver developmentImmunohistochemical expressionDuctal plateEpithelial expressionPortal vasculatureArtery