2024
396 Introduction of CFTR mutations in isogenic induced pluripotent stem cell–derived cholangiocytes and three-dimensional organoids provides pathophysiological information relevant for treatment of CF-related liver disease
Taleb S, Zaman S, Strazzabosco M, Fiorotto R. 396 Introduction of CFTR mutations in isogenic induced pluripotent stem cell–derived cholangiocytes and three-dimensional organoids provides pathophysiological information relevant for treatment of CF-related liver disease. Journal Of Cystic Fibrosis 2024, 23: s208. DOI: 10.1016/s1569-1993(24)01236-0.Peer-Reviewed Original ResearchFRI-162 Analysis of cellular crosstalk in fibrocystic liver disease (PKHD1-/-mouse) reveals a central role for cholangiocytes, neutrophils and chronic biliary infection in disease pathogenesis
Syeda Z, Bauer-Pisani T, Taleb S, Fiorotto R, Strazzabosco M. FRI-162 Analysis of cellular crosstalk in fibrocystic liver disease (PKHD1-/-mouse) reveals a central role for cholangiocytes, neutrophils and chronic biliary infection in disease pathogenesis. Journal Of Hepatology 2024, 80: s697. DOI: 10.1016/s0168-8278(24)01983-4.Peer-Reviewed Original ResearchFRI-155 Introduction of class I-III mutations of CFTR in isogenic human iPSCs-derived cholangiocytes and 3D organoids provides pathophysiological information relevant for treatment of cystic fibrosis-related liver disease (CFLD)
Taleb S, Zaman S, Syeda Z, Strazzabosco M, Fiorotto R. FRI-155 Introduction of class I-III mutations of CFTR in isogenic human iPSCs-derived cholangiocytes and 3D organoids provides pathophysiological information relevant for treatment of cystic fibrosis-related liver disease (CFLD). Journal Of Hepatology 2024, 80: s695. DOI: 10.1016/s0168-8278(24)01978-0.Peer-Reviewed Original ResearchProminent role of gut dysbiosis in the pathogenesis of cystic fibrosis-related liver disease in mice
Bertolini A, Nguyen M, Zehra S, Taleb S, Bauer-Pisani T, Palm N, Strazzabosco M, Fiorotto R. Prominent role of gut dysbiosis in the pathogenesis of cystic fibrosis-related liver disease in mice. Journal Of Hepatology 2024, 81: 429-440. PMID: 38554847, PMCID: PMC11347101, DOI: 10.1016/j.jhep.2024.03.041.Peer-Reviewed Original ResearchCystic fibrosis-related liver diseaseCystic fibrosis transmembrane conductance regulatorCFTR-KO miceDefective cystic fibrosis transmembrane conductance regulatorCFTR-KOIntestinal permeabilityLiver diseaseGut-liver axisGut dysbiosisIncreased morbidityMortality of CF patientsAssociated with increased intestinal permeabilityLiver pathologyDevelopment of cholangiopathyCftr-knockout miceTransmembrane conductance regulatorIncreased intestinal permeabilityTargeted therapeutic strategiesFecal microbiota transferAttenuates liver diseaseExcessive inflammatory responseFITC-dextran assayPresence of neutrophilsActivation of pro-inflammatoryCFTR-knockout
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 LettersCell-matrix interactions control biliary organoid polarity, architecture, and differentiation
Fiorotto R, Mariotti V, Taleb S, Zehra S, Nguyen M, Amenduni M, Strazzabosco M. Cell-matrix interactions control biliary organoid polarity, architecture, and differentiation. Hepatology Communications 2023, 7: e0094. PMID: 36972396, PMCID: PMC10503667, DOI: 10.1097/hc9.0000000000000094.Peer-Reviewed Original ResearchConceptsBiliary organoidsNovel organoid modelImmune cell typesOrganotypic culture systemProinflammatory chemokinesStem cell featuresBiliary epitheliumExtracellular matrixEpithelial permeabilityImportant causeBile acidsBiliary differentiationBile transportHuman liverOrganoid modelsDisease modelsCholangiopathyCell featuresTight junctionsLiverCell typesInternal lumenOrganoidsSingle-cell transcriptomicsPathogenic bacteria
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 levelsScribblesBile 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 StatementsConceptsBile acidsLiver diseaseTherapeutic targetAutoimmune liver diseaseCholestatic liver diseaseBile acid receptorAbsorption of lipidsFat-soluble vitaminsLiver inflammationInflammatory diseasesImmunomodulatory propertiesAcid receptorsInflammationDiseaseReceptorsClinical applicationLiverNutrient metabolismPathway
2021
Novel approaches to liver disease diagnosis and modeling
Oliveira AG, Fiorotto R. Novel approaches to liver disease diagnosis and modeling. Translational Gastroenterology And Hepatology 2021, 6: 19-19. PMID: 33824923, PMCID: PMC7829068, DOI: 10.21037/tgh-20-109.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsNew 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
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 CD8Abnormal 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 elevationRecent Advances in Practical Methods for Liver Cell Biology: A Short Overview
Torres S, Abdullah Z, Brol MJ, Hellerbrand C, Fernandez M, Fiorotto R, Klein S, Königshofer P, Liedtke C, Lotersztajn S, Nevzorova YA, Schierwagen R, Reiberger T, Uschner FE, Tacke F, Weiskirchen R, Trebicka J. Recent Advances in Practical Methods for Liver Cell Biology: A Short Overview. International Journal Of Molecular Sciences 2020, 21: 2027. PMID: 32188134, PMCID: PMC7139397, DOI: 10.3390/ijms21062027.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsLiver cell biologyCell biologyLiver diseaseHepatocellular carcinomaHigh-throughput assaysNon-parenchymal liver cellsSophisticated animal modelsPortal hypertensionLiver pathologyCell isolation techniquesTherapeutic strategiesAnimal modelsStem cellsBiologyPreclinical testingVivo assessmentLiver cellsOrganoid researchVivo methodsNovel opportunitiesDiseaseResearch modalitiesCellsRecent advancesHypertensionCholangiocyte Biology and Pathobiology
Cadamuro M, Fiorotto R, Strazzabosco M. Cholangiocyte Biology and Pathobiology. 2020, 391-407. DOI: 10.1002/9781119436812.ch32.ChaptersBiliary treeEpithelial cellsProliferation of cholangiocytesAmpulla of VaterExtrahepatic biliary treeEpithelial innate immunityToll-like receptorsCanals of HeringBiliary epithelial cellsIntrahepatic branchesLiver damageBiliary systemLiver insultEpithelial barrierInnate immunityCholangiocytesNormal homeostasisLiver lobuleNuclear receptorsCholangiocyte biologyReceptorsCellsVaterMajor roleInsultCholangiocyte biology and pathobiology
Cadamuro M, Fiorotto R, Strazzabosco M. 2020. The liver: Biology and Pathobiology, 6th Edition. Arias IM, Alter HJ, Boyer JL, Cohen DE, Shafritz DA, Thorgeirsson SS, Wolkoff AW Eds. Whiley-Blackwell. ISBN: 978-1-119-43682-9Books
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
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 inhibitorLiver 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 StatementsConceptsLiver 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 fibroblasts