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 ResearchMeSH KeywordsAnimalsDietFatty LiverHepatocytesMaleMiceMice, Inbred C57BLReceptors, NotchSignal TransductionStem CellsConceptsHepatic 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-TBG
2015
Retracted: Posttranslational regulation of polycystin‐2 protein expression as a novel mechanism of cholangiocyte reaction and repair from biliary damage
Spirli C, Villani A, Mariotti V, Fabris L, Fiorotto R, Strazzabosco M. Retracted: Posttranslational regulation of polycystin‐2 protein expression as a novel mechanism of cholangiocyte reaction and repair from biliary damage. Hepatology 2015, 62: 1828-1839. PMID: 26313562, PMCID: PMC4681612, DOI: 10.1002/hep.28138.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBile DuctsCholestasisEpithelial CellsMiceMice, Inbred C57BLProtein Processing, Post-TranslationalTRPP Cation ChannelsConceptsEndoplasmic reticulum stressorsGene expressionAutophagy pathwayExtracellular signal-regulated kinase 1/2 (ERK1/2) pathwayProtein expressionUbiquitin-like proteinSignal-regulated kinase 1/2 pathwayProteasome inhibitor MG-132HIF-1α transcriptional activityKinase 1/2 pathwayProtein kinase APC2 gene expressionPC2 expressionInhibitor MG-132Activation of ERK1/2Transient receptor potential (TRP) channel familyNonselective calcium channelPosttranslational regulationMember 1 proteinPolycystin-2Treatment of cholangiocytesKinase ATranscriptional activityChannel familyMG-132Stimulation 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
Protein kinase a‐dependent pSer675‐β‐catenin, a novel signaling defect in a mouse model of congenital hepatic fibrosis
Spirli C, Locatelli L, Morell CM, Fiorotto R, Morton SD, Cadamuro M, Fabris L, Strazzabosco M. Protein kinase a‐dependent pSer675‐β‐catenin, a novel signaling defect in a mouse model of congenital hepatic fibrosis. Hepatology 2013, 58: 1713-1723. PMID: 23744610, PMCID: PMC3800498, DOI: 10.1002/hep.26554.Peer-Reviewed Original ResearchConceptsAutosomal recessive polycystic kidney diseaseCongenital hepatic fibrosisCaroli's diseaseΒ-cateninHepatic fibrosisRac-1 inhibitionIntrahepatic bile ductsRecessive polycystic kidney diseasePotential therapeutic targetPolycystic kidney diseaseStimulation of cAMPRac-1 activityE-cadherin expressionBile ductKidney diseaseLiver pathologyCystic dysplasiaMouse modelTherapeutic targetTranscriptional activityNuclear translocationDiseasePKA blockerCholangiocytesFibrosisNotch signaling regulates tubular morphogenesis during repair from biliary damage in mice
Fiorotto R, Raizner A, Morell CM, Torsello B, Scirpo R, Fabris L, Spirli C, Strazzabosco M. Notch signaling regulates tubular morphogenesis during repair from biliary damage in mice. Journal Of Hepatology 2013, 59: 124-130. PMID: 23500150, PMCID: PMC3777645, DOI: 10.1016/j.jhep.2013.02.025.Peer-Reviewed Original ResearchMeSH Keywords1-NaphthylisothiocyanateAmyloid Precursor Protein SecretasesAnimalsBile Ducts, IntrahepaticCalcium-Binding ProteinsImmunoglobulin J Recombination Signal Sequence-Binding ProteinIntercellular Signaling Peptides and ProteinsJagged-1 ProteinLiver RegenerationMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutMorphogenesisPyridinesReceptor, Notch2RNA, Small InterferingSerrate-Jagged ProteinsSignal TransductionStem CellsConceptsWild-type miceHepatic progenitor cellsBiliary damageType miceProgenitor cellsDuctular reactionΓ-secretase inhibitor treatmentTubule formationNotch signalingNotch-2 receptorRBP-JkBiliary repairMature ductsLiver-specific defectCKO miceInhibitor treatmentAbstractTextMiceNotch inhibitionNotch-1Jagged-1Notch-2ANITAIMSSOX-9
2011
Dual farnesoid X receptor/TGR5 agonist INT‐767 reduces liver injury in the Mdr2−/− (Abcb4−/−) mouse cholangiopathy model by promoting biliary HCO output
Baghdasaryan A, Claudel T, Gumhold J, Silbert D, Adorini L, Roda A, Vecchiotti S, Gonzalez FJ, Schoonjans K, Strazzabosco M, Fickert P, Trauner M. Dual farnesoid X receptor/TGR5 agonist INT‐767 reduces liver injury in the Mdr2−/− (Abcb4−/−) mouse cholangiopathy model by promoting biliary HCO output. Hepatology 2011, 54: 1303-1312. PMID: 22006858, PMCID: PMC3744065, DOI: 10.1002/hep.24537.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphatasesAnalysis of VarianceAnimalsAnion Transport ProteinsATP Binding Cassette Transporter, Subfamily BBile Acids and SaltsBiliary Tract DiseasesCholic AcidsDisease Models, AnimalLiver DiseasesMaleMiceMice, Inbred C57BLRandom AllocationReceptors, Cytoplasmic and NuclearReceptors, G-Protein-CoupledStatistics, NonparametricConceptsFarnesoid X receptorINT-767Liver injuryChronic cholangiopathiesTGR5 agonistsINT-747Hepatic inflammationINT-777Bile secretionBiliary bile acid outputActivation of FXRNuclear farnesoid X receptorSerum liver enzymesBile acid outputBile acid homeostasisFXR-dependent mannerBile acid synthesisMembrane G protein-coupled receptorsG protein-coupled receptorsLiver transplantationProtein-coupled receptorsBiliary fibrosisAcid outputChow dietTherapeutic optionsLoss 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