2023
Fibroblasts to hepatocytes: A nonstop flight into cell therapy for liver diseases?
Gouon‐Evans V, Fiorotto R. Fibroblasts to hepatocytes: A nonstop flight into cell therapy for liver diseases? Hepatology 2023, 77: 1469-1471. PMID: 35957526, DOI: 10.1002/hep.32725.Commentaries, Editorials and Letters
2022
Bile acids and their receptors: modulators and therapeutic targets in liver inflammation
Bertolini A, Fiorotto R, Strazzabosco M. Bile acids and their receptors: modulators and therapeutic targets in liver inflammation. Seminars In Immunopathology 2022, 44: 547-564. PMID: 35415765, PMCID: PMC9256560, DOI: 10.1007/s00281-022-00935-7.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsBile Acids and SaltsCholestasisHumansInflammationLiverLiver DiseasesReceptors, G-Protein-CoupledConceptsBile acidsLiver diseaseTherapeutic targetAutoimmune liver diseaseCholestatic liver diseaseBile acid receptorAbsorption of lipidsFat-soluble vitaminsLiver inflammationInflammatory diseasesImmunomodulatory propertiesAcid receptorsInflammationDiseaseReceptorsClinical applicationLiverNutrient metabolismPathway
2020
Abnormal Liver Function Tests in Patients With COVID‐19: Relevance and Potential Pathogenesis
Bertolini A, van de Peppel I, Bodewes FAJA, Moshage H, Fantin A, Farinati F, Fiorotto R, Jonker JW, Strazzabosco M, Verkade HJ, Peserico G. Abnormal Liver Function Tests in Patients With COVID‐19: Relevance and Potential Pathogenesis. Hepatology 2020, 72: 1864-1872. PMID: 32702162, PMCID: PMC7404414, DOI: 10.1002/hep.31480.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAbnormal liver function testsLiver function testsCOVID-19 patientsAspartate aminotransferaseFunction testsHospitalized coronavirus disease 2019 (COVID-19) patientsSevere COVID-19 diseaseCoronavirus disease 2019 (COVID-19) patientsElevated liver function testsPre-existing liver diseaseDrug-induced liver injuryCOVID-19Hyper-inflammatory statusAlanine aminotransferase levelsLopinavir/ritonavirOvert liver failureStart of treatmentUse of acetaminophenCause of deathPlasma aspartate aminotransferaseUpper reference limitSARS-CoV-2COVID-19 diseaseAlkaline phosphataseALT elevation
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 growthPathophysiology of Cystic Fibrosis Liver Disease: A Channelopathy Leading to Alterations in Innate Immunity and in Microbiota
Fiorotto R, Strazzabosco M. Pathophysiology of Cystic Fibrosis Liver Disease: A Channelopathy Leading to Alterations in Innate Immunity and in Microbiota. Cellular And Molecular Gastroenterology And Hepatology 2019, 8: 197-207. PMID: 31075352, PMCID: PMC6664222, DOI: 10.1016/j.jcmgh.2019.04.013.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCF-associated liver diseaseLiver diseaseCystic fibrosisInnate immunityCystic fibrosis liver diseaseEpithelial innate immunityCystic fibrosis transmembrane conductance regulatorFibrosis transmembrane conductance regulatorNonpulmonary causesCF adultsTransmembrane conductance regulatorLiver complicationsMutations of CFTRPediatric populationAltered microbiotaIntestinal diseaseBile secretionCF mortalityDiseaseNew drugsConductance regulatorPotential targetLife expectancyBasic defectPathophysiology
2018
Liver diseases in the dish: iPSC and organoids as a new approach to modeling liver diseases
Fiorotto R, Amenduni M, Mariotti V, Fabris L, Spirli C, Strazzabosco M. Liver diseases in the dish: iPSC and organoids as a new approach to modeling liver diseases. Biochimica Et Biophysica Acta (BBA) - Molecular Basis Of Disease 2018, 1865: 920-928. PMID: 30264693, PMCID: PMC6658095, DOI: 10.1016/j.bbadis.2018.08.038.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsDrug Evaluation, PreclinicalGene EditingHumansInduced Pluripotent Stem CellsLiver DiseasesOrganoidsPrimary Cell CultureConceptsLiver diseaseStem cell fieldHepatocyte-like cellsPluripotent stem cellsRegenerative medicineNext-generation toolsSurvival of patientsRecent technological advancesMononuclear blood cellsPotential applicationsGene editingQuality of lifeLiver cell typesDisease modelingCell fieldAdequate cellular modelsLiver transplantationOrgan failureLiver specimensDiseaseStem cellsBlood cellsLiver cellsDrug testingSkin fibroblastsAnimal models for cystic fibrosis liver disease (CFLD)
Fiorotto R, Amenduni M, Mariotti V, Cadamuro M, Fabris L, Spirli C, Strazzabosco M. Animal models for cystic fibrosis liver disease (CFLD). Biochimica Et Biophysica Acta (BBA) - Molecular Basis Of Disease 2018, 1865: 965-969. PMID: 30071276, PMCID: PMC6474816, DOI: 10.1016/j.bbadis.2018.07.026.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCystic fibrosis liver diseaseLiver diseaseAnimal modelsCF animal modelsCystic fibrosisEpithelial innate immunityMore specific treatmentsNovel therapeutic treatmentsDifferent animal modelsLiver manifestationsSevere complicationsPathogenetic factorSpecific treatmentCF miceGut microbiotaInnate immunityTherapeutic treatmentLiver phenotypeDiseaseChloride channelsCystic fibrosis transmembrane conductance regulator (CFTR) channelCFTR expressionHuman diseasesTreatmentApical membrane
2017
Pathophysiologic 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 patternsEmerging concepts in biliary repair and fibrosis
Fabris L, Spirli C, Cadamuro M, Fiorotto R, Strazzabosco M. Emerging concepts in biliary repair and fibrosis. AJP Gastrointestinal And Liver Physiology 2017, 313: g102-g116. PMID: 28526690, PMCID: PMC5582882, DOI: 10.1152/ajpgi.00452.2016.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsReactive ductular cellsBiliary repairBiliary treeDuctular cellsProliferation of cholangiocytesCongenital hepatic fibrosisBiliary fibrosisInflammatory changesBiliary atresiaChronic cholangiopathiesClinical progressionClinical hepatologyHepatic fibrosisLiver repairMajor unmetBiliary epitheliumChronic diseasesChronic damageReparative responseAlagille syndromeLiver pathophysiologyReparative processesFibrosisPathological repairCellular elements
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
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
2009
Mammalian target of rapamycin regulates vascular endothelial growth factor–dependent liver 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. Mammalian target of rapamycin regulates vascular endothelial growth factor–dependent liver cyst growth in polycystin‐2–defective mice. Hepatology 2009, 51: 1778-1788. PMID: 20131403, PMCID: PMC2930014, DOI: 10.1002/hep.23511.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCystsDisease Models, AnimalExtracellular Signal-Regulated MAP KinasesHypoxia-Inducible Factor 1, alpha SubunitInsulin-Like Growth Factor IIntracellular Signaling Peptides and ProteinsLiver DiseasesMicePolycystic Kidney, Autosomal DominantProtein Serine-Threonine KinasesSirolimusTOR Serine-Threonine KinasesTRPP Cation ChannelsVascular Endothelial Growth Factor AConceptsMammalian targetInsulin-like growth factor-1Extracellular signal-regulated kinase 1/2Extracellular signal-regulated kinaseSignal-regulated kinase 1/2Autosomal dominant polycystic kidney diseaseLiver cyst growthVascular endothelial growth factorProtein kinase AInsulin-like growth factor 1 receptorSignal-regulated kinaseGrowth factor 1 receptorVEGF secretionCyst growthMTOR inhibitor rapamycinFactor 1 receptorHIF1alpha accumulationFactor 1 alphaDependent phosphorylationKinase AKinase 1/2P-P70S6KInhibitor rapamycinHypoxia-inducible factor-1 alphaExpression of CC3ERK1/2-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
2003
Cytokine-stimulated nitric oxide production inhibits adenylyl cyclase and cAMP-dependent secretion in cholangiocytes
Spirlì C, Fabris L, Duner E, Fiorotto R, Ballardini G, Roskams T, Larusso NF, Sonzogni A, Okolicsanyi L, Strazzabosco M. Cytokine-stimulated nitric oxide production inhibits adenylyl cyclase and cAMP-dependent secretion in cholangiocytes. Gastroenterology 2003, 124: 737-753. PMID: 12612912, DOI: 10.1053/gast.2003.50100.Peer-Reviewed Original ResearchMeSH KeywordsAdenylyl Cyclase InhibitorsAdenylyl CyclasesAnimalsBile DuctsBile Ducts, IntrahepaticCell LineCyclic AMPDrug SynergismGene ExpressionHumansInterferon-gammaIntracellular FluidIon TransportLiver DiseasesNitratesNitric OxideNitric Oxide DonorsNitric Oxide SynthaseNitric Oxide Synthase Type IINitritesRatsTumor Necrosis Factor-alphaConceptsPrimary sclerosing cholangitisProinflammatory cytokinesBiliary epitheliumAdenylyl cyclaseHuman chronic liver diseaseInducible nitric oxide synthaseChronic liver diseaseSecretory mechanismInhibition of ACNitric oxide synthaseTumor necrosis factorDependent fluid secretionReactive nitrogen oxide speciesCAMP-dependent secretionNOS-2 inhibitorCystic fibrosis transmembrane conductance regulatorCAMP-dependent ClDuctular cholestasisProgressive cholestasisSclerosing cholangitisLiver diseaseCholestatic effectLiver damageBile productionNOS2 induction