2021
New insights on the role of vascular endothelial growth factor in biliary pathophysiology
Mariotti V, Fiorotto R, Cadamuro M, Fabris L, Strazzabosco M. New insights on the role of vascular endothelial growth factor in biliary pathophysiology. JHEP Reports 2021, 3: 100251. PMID: 34151244, PMCID: PMC8189933, DOI: 10.1016/j.jhepr.2021.100251.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsVEGF/VEGFRCell biologyVascular endothelial growth factorCritical biological processesEpithelial cell biologyHIF1α-dependent mechanismEndothelial cell biologyEndothelial growth factorEpithelial cellsGrowth factorAccessory proteinsLiver repair processesCystic cellsBiological processesKinase receptorsVEGFR-2 receptorCell typesRole of VEGFBiliary developmentBiliary pathophysiologyDevelopment of cirrhosisChronic biliary diseaseBile duct proliferationPolycystic liver diseaseWound healing response
2019
Pathobiology of inherited biliary diseases: a roadmap to understand acquired liver diseases
Fabris L, Fiorotto R, Spirli C, Cadamuro M, Mariotti V, Perugorria MJ, Banales JM, Strazzabosco M. Pathobiology of inherited biliary diseases: a roadmap to understand acquired liver diseases. Nature Reviews Gastroenterology & Hepatology 2019, 16: 497-511. PMID: 31165788, PMCID: PMC6661007, DOI: 10.1038/s41575-019-0156-4.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCystic fibrosis-related liver diseaseFibropolycystic liver diseaseLiver diseasePolycystic liver diseaseBiliary repairAlagille syndromeEpithelial toll-like receptor 4Toll-like receptor 4Acquired liver diseasesGut-derived productsPrimary sclerosing cholangitisDuct epithelial cellsSclerosing cholangitisΒ-catenin signalingPortal fibrosisBiliary diseaseIL-1βUnknown etiologyDependent cytokinesReceptor 4Peribiliary inflammationRole of NotchCholangiopathyNovel treatmentsCyst growth
2016
Adenylyl 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 mice
2012
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
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
2010
Cholangiocyte Biology as Relevant to Cystic Liver Diseases
Lecchi S, Fabris L, Spirli C, Cadamuro M, Fiorotto R, Strazzabosco M. Cholangiocyte Biology as Relevant to Cystic Liver Diseases. Clinical Gastroenterology 2010, 23-43. DOI: 10.1007/978-1-60327-524-8_2.ChaptersLiver cystsLiver diseaseSevere life-threatening complicationsIntrahepatic bile duct epitheliumComplex intercellular signalingCystic liver diseaseProgressive cyst growthLife-threatening complicationsEpithelial cellsBile duct epitheliumIntrahepatic biliary treePolycystic liver diseaseExcessive fluid secretionRenal tubule epitheliumRecessive formExtracellular matrix remodelingBiliary treeBiliary epitheliumCystic diseaseDuct epitheliumCyst expansionCyst growthAutocrine mechanismTubule epitheliumHereditary disorder
2009
ERK1/2-Dependent Vascular Endothelial Growth Factor Signaling Sustains Cyst Growth in Polycystin-2 Defective Mice
Spirli C, Okolicsanyi S, Fiorotto R, Fabris L, Cadamuro M, Lecchi S, Tian X, Somlo S, Strazzabosco M. ERK1/2-Dependent Vascular Endothelial Growth Factor Signaling Sustains Cyst Growth in Polycystin-2 Defective Mice. Gastroenterology 2009, 138: 360-371.e7. PMID: 19766642, PMCID: PMC3000794, DOI: 10.1053/j.gastro.2009.09.005.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedCyclic AMP-Dependent Protein KinasesCystsHypoxia-Inducible Factor 1, alpha SubunitIndolesLiver DiseasesMAP Kinase Signaling SystemMiceMice, KnockoutMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3PhenotypePhosphorylationProliferating Cell Nuclear AntigenProtein Kinase InhibitorsPyrrolesRepressor ProteinsTRPP Cation ChannelsTumor Suppressor ProteinsVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2ConceptsVascular endothelial growth factorPolycystic liver diseaseVEGF secretionLiver cystsLiver diseaseVEGFR-2Cyst growthLiver/body weight ratioAdult dominant polycystic kidney diseaseParacrine vascular endothelial growth factorSecretion of VEGFHIF-1alphaBody weight ratioEffects of VEGFAutocrine vascular endothelial growth factorDominant polycystic kidney diseaseExpression of pERKVascular endothelial growth factor signalingPhosphorylated VEGFR-2Liver cyst growthEndothelial growth factorPolycystic kidney diseaseCyst epithelial cellsExtracellular signal-regulated kinase 1/2Hypoxia-inducible factor
2006
Effects of angiogenic factor overexpression by human and rodent cholangiocytes in polycystic liver diseases
Fabris L, Cadamuro M, Fiorotto R, Roskams T, Spirlì C, Melero S, Sonzogni A, Joplin RE, Okolicsanyi L, Strazzabosco M. Effects of angiogenic factor overexpression by human and rodent cholangiocytes in polycystic liver diseases. Hepatology 2006, 43: 1001-1012. PMID: 16628643, DOI: 10.1002/hep.21143.Peer-Reviewed Original ResearchConceptsAutosomal dominant polycystic kidney diseaseVascular endothelial growth factorPolycystic liver diseaseAng-1Liver diseaseDuctal platePortal vasculatureAng-2 gene expressionTie-2Expression of VEGFEmbryonic ductal plateDuctal plate cellsEffects of VEGFDominant polycystic kidney diseaseLiver cyst growthEndothelial growth factorAutocrine proliferative effectsPolycystic kidney diseaseLiver involvementADPKD mouse modelBiliary cystsCaroli's diseaseKidney diseaseADPKD patientsAng-2