2022
Molecular determinants of peri‐apical targeting of inositol 1,4,5‐trisphosphate receptor type 3 in cholangiocytes
Rodrigues MA, Gomes DA, Fiorotto R, Guerra MT, Weerachayaphorn J, Bo T, Sessa WC, Strazzabosco M, Nathanson MH. Molecular determinants of peri‐apical targeting of inositol 1,4,5‐trisphosphate receptor type 3 in cholangiocytes. Hepatology Communications 2022, 6: 2748-2764. PMID: 35852334, PMCID: PMC9512452, DOI: 10.1002/hep4.2042.Peer-Reviewed Original ResearchConceptsLipid raftsCaveolin-1Intact lipid raftsType 3 inositol trisphosphate receptorApical regionC-terminal amino acidsTrisphosphate receptor type 3Madin-Darby canine kidney cellsCanine kidney cellsFluorescence microscopy techniquesInositol trisphosphate receptorApical localizationTrisphosphate receptorHeavy chain 9Molecular determinantsChemical disruptionAmino acidsITPR3RaftsKidney cellsIntracellular CaFinal common eventReceptor type 3Release channelMYH9Dysregulation of the Scribble/YAP/β‐catenin axis sustains the fibroinflammatory response in a PKHD1−/− mouse model of congenital hepatic fibrosis
Fabris L, Milani C, Fiorotto R, Mariotti V, Kaffe E, Seller B, Sonzogni A, Strazzabosco M, Cadamuro M. Dysregulation of the Scribble/YAP/β‐catenin axis sustains the fibroinflammatory response in a PKHD1−/− mouse model of congenital hepatic fibrosis. The FASEB Journal 2022, 36: e22364. PMID: 35593740, PMCID: PMC9150862, DOI: 10.1096/fj.202101924r.Peer-Reviewed Original ResearchConceptsYes-associated proteinPlanar cell polarityΒ-cateninΒ-catenin axisYAP nuclear importRole of ScribbleNuclear translocationYAP/TAZΒ-catenin signalingCell polarityNuclear importCyst cellsNuclear expressionScribble expressionΒ-catenin nuclear expressionConditional deletionGenetic defectsTissue growth factor expressionIntegrin β6Connective tissue growth factor expressionCyst growthExpressionCystic cholangiocytesMRNA levelsScribbles
2020
IL-17A/F enable cholangiocytes to restrict T cell-driven experimental cholangitis by upregulating PD-L1 expression
Stein S, Henze L, Poch T, Carambia A, Krech T, Preti M, Schuran FA, Reich M, Keitel V, Fiorotto R, Strazzabosco M, Fischer L, Li J, Müller LM, Wagner J, Gagliani N, Herkel J, Schwinge D, Schramm C. IL-17A/F enable cholangiocytes to restrict T cell-driven experimental cholangitis by upregulating PD-L1 expression. Journal Of Hepatology 2020, 74: 919-930. PMID: 33197512, PMCID: PMC8778963, DOI: 10.1016/j.jhep.2020.10.035.Peer-Reviewed Original ResearchConceptsIL-17A/FIL-17PD-L1T cellsOT-1Mouse modelAutoimmune cholestatic liver diseaseCell death ligand 1Cholangiocyte organoidsMajor histocompatibility complex IBile duct inflammationAntigen-specific CD8Bile duct injuryPD-L1 expressionDeath ligand 1Driver of inflammationTreatment of cholangitisCholestatic liver diseaseResponse of miceImportant protective effectDuct inflammationExperimental cholangitisDuct injuryAdoptive transferCytotoxic CD8
2018
Platelet-derived growth factor-D enables liver myofibroblasts to promote tumor lymphangiogenesis in cholangiocarcinoma
Cadamuro M, Brivio S, Mertens J, Vismara M, Moncsek A, Milani C, Fingas C, Cristina Malerba M, Nardo G, Dall'Olmo L, Milani E, Mariotti V, Stecca T, Massani M, Spirli C, Fiorotto R, Indraccolo S, Strazzabosco M, Fabris L. Platelet-derived growth factor-D enables liver myofibroblasts to promote tumor lymphangiogenesis in cholangiocarcinoma. Journal Of Hepatology 2018, 70: 700-709. PMID: 30553841, PMCID: PMC10878126, DOI: 10.1016/j.jhep.2018.12.004.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBile Duct NeoplasmsCancer-Associated FibroblastsCell Line, TumorCholangiocarcinomaDisease Models, AnimalEndothelial CellsHeterograftsHumansImatinib MesylateLiverLymphangiogenesisLymphokinesMaleMiceMice, SCIDMyofibroblastsPlatelet-Derived Growth FactorProtein Kinase InhibitorsRatsRats, Inbred F344Receptor, Platelet-Derived Growth Factor betaVascular Endothelial Growth Factor AVascular Endothelial Growth Factor CConceptsCancer-associated fibroblastsLymphatic endothelial cellsCholangiocarcinoma specimensMetastatic spreadStromal reactionLiver myofibroblastsGrowth factorExtensive stromal reactionLymph node metastasisEarly metastatic spreadLevels of VEGFBH3 mimetic navitoclaxPlatelet-derived growth factorRole of PDGFVascular growth factorsTumor-associated lymphangiogenesisVEGF-C secretionTransendothelial electric resistanceCholangiocarcinoma invasivenessHuman lymphatic endothelial cellsCurative therapyNode metastasisBiliary treeEarly metastasisPDGFRβ inhibitorβ‐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
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-TBGAnimal models of biliary injury and altered bile acid metabolism
Mariotti V, Strazzabosco M, Fabris L, Calvisi DF. Animal models of biliary injury and altered bile acid metabolism. Biochimica Et Biophysica Acta (BBA) - Molecular Basis Of Disease 2017, 1864: 1254-1261. PMID: 28709963, PMCID: PMC5764833, DOI: 10.1016/j.bbadis.2017.06.027.Peer-Reviewed Original ResearchConceptsBile acid metabolismBiliary injuryMouse modelAnimal modelsDistinct immune systemCholestatic liver injuryAcid metabolismJesus BanalesMarco MarzioniNicholas LaRussoPeter JansenBiliary repairLiver injuryDuctular reactionLiver repairObstructive cholestasisDisease progressionPeribiliary inflammationMain phenotypic featuresBiliary dysgenesisViral infectionImmune systemLiver homeostasisLiver phenotypeHuman setting
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 miceLow-Dose Paclitaxel Reduces S100A4 Nuclear Import to Inhibit Invasion and Hematogenous Metastasis of Cholangiocarcinoma
Cadamuro M, Spagnuolo G, Sambado L, Indraccolo S, Nardo G, Rosato A, Brivio S, Caslini C, Stecca T, Massani M, Bassi N, Novelli E, Spirli C, Fabris L, Strazzabosco M. Low-Dose Paclitaxel Reduces S100A4 Nuclear Import to Inhibit Invasion and Hematogenous Metastasis of Cholangiocarcinoma. Cancer Research 2016, 76: 4775-4784. PMID: 27328733, PMCID: PMC4987167, DOI: 10.1158/0008-5472.can-16-0188.Peer-Reviewed Original ResearchMeSH KeywordsActive Transport, Cell NucleusAnimalsAntineoplastic Agents, PhytogenicBile Duct NeoplasmsBlotting, WesternCell Line, TumorCell ProliferationCholangiocarcinomaHumansMiceMice, SCIDNeoplasm InvasivenessNeoplasm MetastasisPaclitaxelS100 Calcium-Binding Protein A4SumoylationXenograft Model Antitumor AssaysConceptsLow-dose paclitaxelNuclear S100A4Nuclear expressionSCID mouse xenograft modelPrimary liver cancerLocal tumor growthEGI-1 cellsCandidate therapeutic targetMouse xenograft modelMMP-9 secretionCholangiocarcinoma cell linesCholangiocarcinoma invasivenessLung disseminationMT1-MMP expressionCalcium binding proteinDismal prognosisRate of proliferationMetastatic spreadLiver cancerTumor massPaclitaxel treatmentXenograft modelTherapeutic targetTreatment opportunitiesMetastatic progressionMacrophage 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
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 ResearchConceptsEndoplasmic 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 blockerCholangiocytesFibrosisPlatelet‐derived growth factor‐D and Rho GTPases regulate recruitment of cancer‐associated fibroblasts in cholangiocarcinoma
Cadamuro M, Nardo G, Indraccolo S, Dall'Olmo L, Sambado L, Moserle L, Franceschet I, Colledan M, Massani M, Stecca T, Bassi N, Morton S, Spirli C, Fiorotto R, Fabris L, Strazzabosco M. Platelet‐derived growth factor‐D and Rho GTPases regulate recruitment of cancer‐associated fibroblasts in cholangiocarcinoma. Hepatology 2013, 58: 1042-1053. PMID: 23505219, PMCID: PMC3732815, DOI: 10.1002/hep.26384.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBenzamidesBile Duct NeoplasmsBile Ducts, IntrahepaticCell Line, TumorCell MovementCell ProliferationCells, CulturedCholangiocarcinomaEpithelial-Mesenchymal TransitionFibroblastsHeterograftsHumansImatinib MesylateIn Vitro TechniquesLymphokinesMaleMiceMice, SCIDPiperazinesPlatelet-Derived Growth FactorPyrimidinesRho GTP-Binding ProteinsSignal TransductionConceptsCancer-associated fibroblastsPlatelet-derived growth factorEpithelial-mesenchymal transitionCCA cellsSecretion of PDGFRole of PDGFGrowth factorAbundant stromal reactionAlpha-smooth muscle actinPDGF-D expressionNovel therapeutic approachesPotential therapeutic targetSmooth muscle actinCCA cell linesPDGF-D signalingFibroblast migrationC-Jun N-terminal kinaseEMT biomarkersImmunodeficient miceStromal reactionTherapeutic approachesStroma interactionsTherapeutic targetCholangiocarcinomaMesenchymal markersNotch 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
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 monophosphateERKAltered store operated calcium entry increases cyclic 3′,5′‐adenosine monophosphate production and extracellular signal‐regulated kinases 1 and 2 phosphorylation in polycystin‐2‐defective cholangiocytes
Spirli C, Locatelli L, Fiorotto R, Morell CM, Fabris L, Pozzan T, Strazzabosco M. Altered store operated calcium entry increases cyclic 3′,5′‐adenosine monophosphate production and extracellular signal‐regulated kinases 1 and 2 phosphorylation in polycystin‐2‐defective cholangiocytes. Hepatology 2012, 55: 856-868. PMID: 21987453, PMCID: PMC3272110, DOI: 10.1002/hep.24723.Peer-Reviewed Original ResearchMeSH KeywordsAdenylyl CyclasesAnimalsBile DuctsCalciumCalcium ChannelsCalcium SignalingCells, CulturedCyclic AMPCyclic AMP-Dependent Protein KinasesHomeostasisMembrane GlycoproteinsMiceMice, KnockoutMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Models, AnimalPhosphorylationSignal TransductionStromal Interaction Molecule 1TRPP Cation ChannelsVascular Endothelial Growth Factor AConceptsSensor stromal interaction molecule 1Adenylyl cyclase type 6Extracellular signal-regulated kinases 1Signal-regulated kinases 1Overproduction of cAMPStromal interaction molecule 1Orai channelsWild-type miceSOCE activationCAMP productionRapamycin (mTOR) signalingKinase 1ERK pathwayERK1/2 activationHuman diseasesWT cellsMammalian targetDependent activationSTIM-1CAMP/Inappropriate activationCyst growthCystic cholangiocytesPolycystic liver diseaseActivation
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 options