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
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 blockerCholangiocytesFibrosis
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