2021
The Neglected Role of Bile Duct Epithelial Cells in NASH
Cadamuro M, Lasagni A, Sarcognato S, Guido M, Fabris R, Strazzabosco M, Strain AJ, Simioni P, Villa E, Fabris L. The Neglected Role of Bile Duct Epithelial Cells in NASH. Seminars In Liver Disease 2021, 42: 034-047. PMID: 34794182, DOI: 10.1055/s-0041-1739455.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseNonalcoholic steatohepatitisLiver diseaseInsulin resistancePrevalent liver diseaseBile duct epithelial cellsFatty liver diseaseSubset of patientsCommon pathogenetic mechanismDuct epithelial cellsMultiple biological effectsFibro-inflammationHepatic manifestationNAFLD patientsPortal fibrosisMetabolic syndromeBile ductDuctular reactionDisease progressionPathogenetic mechanismsLiver cancerMetabolic alterationsProgenitor cell compartmentEpithelial cellsDiseaseAn international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs
Cordell H, Fryett J, Ueno K, Darlay R, Aiba Y, Hitomi Y, Kawashima M, Nishida N, Khor S, Gervais O, Kawai Y, Nagasaki M, Tokunaga K, Tang R, Shi Y, Li Z, Juran B, Atkinson E, Gerussi A, Carbone M, Asselta R, Cheung A, de Andrade M, Baras A, Horowitz J, Ferreira M, Sun D, Jones D, Flack S, Spicer A, Mulcahy V, Byan J, Han Y, Sandford R, Lazaridis K, Amos C, Hirschfield G, Seldin M, Invernizzi P, Siminovitch K, Ma X, Nakamura M, Mells G, Consortia P, Consortium C, Siminovitch K, Mason A, Vincent C, Xie G, Zhang J, Consortium C, Tang R, Ma X, Li Z, Shi Y, Group I, Affronti A, Almasio P, Alvaro D, Andreone P, Andriulli A, Azzaroli F, Battezzati P, Benedetti A, Bragazzi M, Brunetto M, Bruno S, Calvaruso V, Cardinale V, Casella G, Cazzagon N, Ciaccio A, Coco B, Colli A, Colloredo G, Colombo M, Colombo S, Cristoferi L, Cursaro C, Crocè L, Crosignani A, D’Amato D, Donato F, Elia G, Fabris L, Fagiuoli S, Ferrari C, Floreani A, Galli A, Giannini E, Grattagliano I, Lampertico P, Lleo A, Malinverno F, Mancuso C, Marra F, Marzioni M, Massironi S, Mattalia A, Miele L, Milani C, Morini L, Morisco F, Muratori L, Muratori P, Niro G, O’Donnell S, Picciotto A, Portincasa P, Rigamonti C, Ronca V, Rosina F, Spinzi G, Strazzabosco M, Tarocchi M, Tiribelli C, Toniutto P, Valenti L, Vinci M, Zuin M, Consortium J, Nakamura H, Abiru S, Nagaoka S, Komori A, Yatsuhashi H, Ishibashi H, Ito M, Migita K, Ohira H, Katsushima S, Naganuma A, Sugi K, Komatsu T, Mannami T, Matsushita K, Yoshizawa K, Makita F, Nikami T, Nishimura H, Kouno H, Kouno H, Ota H, Komura T, Nakamura Y, Shimada M, Hirashima N, Komeda T, Ario K, Nakamuta M, Yamashita T, Furuta K, Kikuchi M, Naeshiro N, Takahashi H, Mano Y, Tsunematsu S, Yabuuchi I, Shimada Y, Yamauchi K, Sugimoto R, Sakai H, Mita E, Koda M, Tsuruta S, Kamitsukasa H, Sato T, Masaki N, Kobata T, Fukushima N, Ohara Y, Muro T, Takesaki E, Takaki H, Yamamoto T, Kato M, Nagaoki Y, Hayashi S, Ishida J, Watanabe Y, Kobayashi M, Koga M, Saoshiro T, Yagura M, Hirata K, Tanaka A, Takikawa H, Zeniya M, Abe M, Onji M, Kaneko S, Honda M, Arai K, Arinaga-Hino T, Hashimoto E, Taniai M, Umemura T, Joshita S, Nakao K, Ichikawa T, Shibata H, Yamagiwa S, Seike M, Honda K, Sakisaka S, Takeyama Y, Harada M, Senju M, Yokosuka O, Kanda T, Ueno Y, Kikuchi K, Ebinuma H, Himoto T, Yasunami M, Murata K, Mizokami M, Kawata K, Shimoda S, Miyake Y, Takaki A, Yamamoto K, Hirano K, Ichida T, Ido A, Tsubouchi H, Chayama K, Harada K, Nakanuma Y, Maehara Y, Taketomi A, Shirabe K, Soejima Y, Mori A, Yagi S, Uemoto S, Egawa H, Tanaka T, Yamashiki N, Tamura S, Sugawara Y, Kokudo N, Consortium P, Atkinson E, de Andrade M, Chalasani N, Luketic V, Odin J, Chopra K, Baras A, Horowitz J, Abecasis G, Cantor M, Coppola G, Economides A, Lotta L, Overton J, Reid J, Shuldiner A, Beechert C, Forsythe C, Fuller E, Gu Z, Lattari M, Lopez A, Schleicher T, Padilla M, Toledo K, Widom L, Wolf S, Pradhan M, Manoochehri K, Ulloa R, Bai X, Balasubramanian S, Barnard L, Blumenfeld A, Eom G, Habegger L, Hawes A, Khalid S, Maxwell E, Salerno W, Staples J, Jones M, Mitnaul L, Consortium U, Sturgess R, Healey C, Yeoman A, Gunasekera A, Kooner P, Kapur K, Sathyanarayana V, Kallis Y, Subhani J, Harvey R, McCorry R, Rooney P, Ramanaden D, Evans R, Mathialahan T, Gasem J, Shorrock C, Bhalme M, Southern P, Tibble J, Gorard D, Jones S, Mells G, Mulcahy V, Srivastava B, Foxton M, Collins C, Elphick D, Karmo M, Porras-Perez F, Mendall M, Yapp T, Patel M, Ede R, Sayer J, Jupp J, Fisher N, Carter M, Koss K, Shah J, Piotrowicz A, Scott G, Grimley C, Gooding I, Williams S, Tidbury J, Lim G, Cheent K, Levi S, Mansour D, Beckley M, Hollywood C, Wong T, Marley R, Ramage J, Gordon H, Ridpath J, Ngatchu T, Grover V, Shidrawi R, Abouda G, Corless L, Narain M, Rees I, Brown A, Taylor-Robinson S, Wilkins J, Grellier L, Banim P, Das D, Heneghan M, Curtis H, Matthews H, Mohammed F, Aldersley M, Srirajaskanthan R, Walker G, McNair A, Sharif A, Sen S, Bird G, Prince M, Prasad G, Kitchen P, Barnardo A, Oza C, Sivaramakrishnan N, Gupta P, Shah A, Evans C, Saha S, Pollock K, Bramley P, Mukhopadhya A, Barclay S, McDonald N, Bathgate A, Palmer K, Dillon J, Rushbrook S, Przemioslo R, McDonald C, Millar A, Tai C, Mitchell S, Metcalf J, Shaukat S, Ninkovic M, Shmueli U, Davis A, Naqvi A, Lee T, Ryder S, Collier J, Klass H, Cramp M, Sharer N, Aspinall R, Ghosh D, Douds A, Booth J, Williams E, Hussaini H, Christie J, Mann S, Thorburn D, Marshall A, Patanwala I, Ala A, Maltby J, Matthew R, Corbett C, Vyas S, Singhal S, Gleeson D, Misra S, Butterworth J, George K, Harding T, Douglass A, Mitchison H, Panter S, Shearman J, Bray G, Roberts M, Butcher G, Forton D, Mahmood Z, Cowan M, Das D, Ch’ng C, Rahman M, Whatley G, Wesley E, Mandal A, Jain S, Pereira S, Wright M, Trivedi P, Gordon F, Unitt E, Palejwala A, Austin A, Vemala V, Grant A, Higham A, Brind A, Mathew R, Cox M, Ramakrishnan S, King A, Whalley S, Fraser J, Thomson S, Bell A, Wong V, Kia R, Gee I, Keld R, Ransford R, Gotto J, Millson C. An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs. Journal Of Hepatology 2021, 75: 572-581. PMID: 34033851, PMCID: PMC8811537, DOI: 10.1016/j.jhep.2021.04.055.Peer-Reviewed Original ResearchConceptsChronic liver diseaseBiliary cholangitisLiver diseaseSmall intrahepatic bile ductsTreatment of PBCPrimary biliary cholangitisIntrahepatic bile ductsAdditional risk lociRisk lociPattern recognition receptorsLicensed medicationsT helperAutoimmune destructionEast Asian cohortsAutoimmune disordersBile ductAsian cohortEuropean cohortInadequate responseNovel therapiesDrug efficacy screeningHealthy individualsGenome-wide association studiesNumerous risk lociRecognition receptorsFibrocystic liver disease: novel concepts and translational perspectives
Lasagni A, Cadamuro M, Morana G, Fabris L, Strazzabosco M. Fibrocystic liver disease: novel concepts and translational perspectives. Translational Gastroenterology And Hepatology 2021, 6: 26-26. PMID: 33824930, PMCID: PMC7838530, DOI: 10.21037/tgh-2020-04.Peer-Reviewed Original ResearchFibrocystic liver diseaseAutosomal recessive polycystic kidney diseaseIntrahepatic bile ductsBile ductPeribiliary fibrosisLarge intrahepatic bile ductsSmall intrahepatic bile ductsBile duct dilationEmbryonic ductal plateTargeted medical therapyRenal function impairmentMain clinical manifestationsRecessive polycystic kidney diseaseSpectrum of disordersHepatic disease 1Polycystic kidney diseaseBiliary microhamartomasLiver transplantationPortal hypertensionRecurrent cholangitisBiliary changesBiliary cystsDuct dilationMedical therapySurgical treatmentCongenital Cystic Lesions of the Biliary Tree
Lasagni A, Morana G, Strazzabosco M, Fabris L, Cadamuro M. Congenital Cystic Lesions of the Biliary Tree. 2021, 19-46. DOI: 10.1007/978-3-030-65908-0_2.Peer-Reviewed Original ResearchFibropolycystic liver diseasePolycystic liver diseaseFibrocystic liver diseaseHepatorenal fibrocystic diseaseIntrahepatic bile ductsCholedochal cystLiver diseaseBile ductBiliary treeLarge intrahepatic bile ductsSmall intrahepatic bile ductsBile duct dilationRenal function impairmentEarly surgical interventionOnly curative approachCongenital cystic lesionsExtrahepatic bile ductDuctal plate malformationRecessive polycystic kidney diseasePotential therapeutic targetSpectrum of disordersGrowth of cystsPolycystic kidney diseaseBiliary microhamartomasLiver transplantation
2019
Molecular Pathogenesis: From Inflammation and Cholestasis to a Microenvironment-Driven Tumor
Milani E, Strazzabosco M, Fabris L, Cadamuro M. Molecular Pathogenesis: From Inflammation and Cholestasis to a Microenvironment-Driven Tumor. 2019, 167-182. DOI: 10.1007/978-3-030-22258-1_12.Peer-Reviewed Original ResearchTumor reactive stromaIntrahepatic cholangiocarcinomaReactive stromaTumor-infiltrating lymphocytesPrimary liver cancerTumor-associated macrophagesCancer-associated fibroblastsMalignant bile ductPro-invasive functionMain stromal cell typesBiliary lesionsProgenitor stem cellsBile ductChronic inflammationStromal cell typesPortal tractsTumor overgrowthLiver cancerPathogenetic sequenceMalignant transformationParacrine factorsTumor microenvironmentCholestasisOncogenic effectsInflammationFibrocystic Liver Disease
Cristoferi L, Morana G, Strazzabosco M, Fabris L. Fibrocystic Liver Disease. 2019, 201-218. DOI: 10.1007/978-3-319-96400-3_11.Peer-Reviewed Original ResearchHepatorenal fibrocystic diseaseCongenital hepatic fibrosisFibrocystic liver diseaseLiver diseaseCaroli's diseaseCholedochal cystEnd-stage liver diseaseBiliary duct dilationEmbryonic ductal plateAutosomal recessive polycystic kidney diseaseIntrahepatic bile ductsRecessive polycystic kidney diseasePolycystic kidney diseaseLiver transplantationDuct dilationHepatic involvementMultidisciplinary managementRenal diseaseMultiorgan involvementClinical manifestationsBile ductFibrocystic diseaseKidney diseaseBiliary treeHepatic fibrosisCholangiocyte pathobiology
Banales JM, Huebert RC, Karlsen T, Strazzabosco M, LaRusso NF, Gores GJ. Cholangiocyte pathobiology. Nature Reviews Gastroenterology & Hepatology 2019, 16: 269-281. PMID: 30850822, PMCID: PMC6563606, DOI: 10.1038/s41575-019-0125-y.Peer-Reviewed Original ResearchConceptsCholangiocyte pathobiologyNew disease-modifying therapiesLiver regenerationRole of cholangiocytesAdvanced liver failureDisease-modifying therapiesExtrahepatic bile ductChronic disease statesAdaptive immune responsesReactive ductular cellsLiver failureBiliary tractLiver diseaseBile ductBile productionImmune responseHepatocyte regenerationImmune systemDuctular cellsCholangiopathyDisease statesCholangiocytesEpithelial cellsAnatomic nicheRepair response
2018
Fibropolycystic Liver Diseases and Congenital Biliary Abnormalities
Hadžić N, Strazzabosco M. Fibropolycystic Liver Diseases and Congenital Biliary Abnormalities. 2018, 308-327. DOI: 10.1002/9781119237662.ch16.Peer-Reviewed Original ResearchFibropolycystic liver diseaseLiver diseasePolycystic kidney diseaseKidney diseaseAutosomal recessive polycystic kidney diseaseAutosomal dominant polycystic kidney diseaseFibrotic liver diseasePolycystic liver diseaseRecessive polycystic kidney diseaseDominant polycystic kidney diseaseCongenital biliary abnormalitiesBiliary microhamartomasPathogenetic pointCholedochal cystBiliary tractBiliary abnormalitiesBile ductCystic lesionsRenal abnormalitiesClinical reasonsCongenital anomaliesLiver parenchymaDiseaseHeterogeneous groupAbnormalities
2017
The Healthy Biliary Tree: Cellular and Immune Biology
Cadamuro M, Fabris L, Strazzabosco M. The Healthy Biliary Tree: Cellular and Immune Biology. 2017, 17-41. DOI: 10.1007/978-3-319-50168-0_2.Peer-Reviewed Original ResearchBiliary innate immunityToll-like receptorsPathogen-associated molecular patternsBiliary treeLiver diseaseCystic fibrosis-related liver diseaseInnate immunityCystic fibrosis liver diseaseAntigen-presenting cellsBiliary epithelial cellsLiver injuryBile ductBiliary diseaseLiver damageInflammatory responseImmune biologyFirst defense lineProinflammatory behaviorSecretory activityMolecular patternsCholangiocytesEpithelial cellsDiseaseCholangiopathyEvidence highlights
2015
Epithelial-to-Mesenchymal Transition and Cancer Invasiveness: What Can We Learn from Cholangiocarcinoma?
Brivio S, Cadamuro M, Fabris L, Strazzabosco M. Epithelial-to-Mesenchymal Transition and Cancer Invasiveness: What Can We Learn from Cholangiocarcinoma? Journal Of Clinical Medicine 2015, 4: 2028-2041. PMID: 26703747, PMCID: PMC4693158, DOI: 10.3390/jcm4121958.Peer-Reviewed Original ResearchMesenchymal transitionAbundant stromal reactionEarly metastatic behaviorPrimary liver cancerEMT-like changesPotential therapeutic targetPro-invasive phenotypeSpecific disease mechanismsDismal prognosisBile ductChronic inflammationEMT biomarkersEpithelial malignanciesStromal reactionLiver cancerTumor stromaTherapeutic targetCholangiocarcinomaNew biomarkersTumor metastatizationMetastatic behaviorCCA cellsTherapeutic opportunitiesTumor microenvironmentStromal cells
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 blockerCholangiocytesFibrosisVascular biology of the biliary epithelium
Morell CM, Fabris L, Strazzabosco M. Vascular biology of the biliary epithelium. Journal Of Gastroenterology And Hepatology 2013, 28: 26-32. PMID: 23855292, PMCID: PMC3721432, DOI: 10.1111/jgh.12022.Peer-Reviewed Original ResearchMeSH KeywordsAngiopoietinsAnimalsAutocrine CommunicationBile Duct DiseasesBile Ducts, IntrahepaticEpithelial CellsEpitheliumHumansLiverLiver Diseases, AlcoholicLiver RegenerationNeovascularization, PathologicParacrine CommunicationPlatelet-Derived Growth FactorRatsSignal TransductionVascular Endothelial Growth Factor AConceptsBile ductIntrahepatic bile ductsHepatic arteryPeribiliary plexusUnderlying molecular mechanismsArterial supplyLiver repairNormal organ physiologyLiver pathophysiologyVascular cell typesPathophysiological settingsVascular structuresStrong associationVascular biologyDifferent vascular cell typesCholangiocytesAngiogenic signalsLiver developmentCell typesMolecular mechanismsOrgan physiologyDuctAssociationCross talkIsolation and characterization of biliary epithelial and stromal cells from resected human cholangiocarcinoma: A novel in vitro model to study tumor-stroma interactions
MASSANI M, STECCA T, FABRIS L, CARATOZZOLO E, RUFFOLO C, FURLANETTO A, MORTON S, CADAMURO M, STRAZZABOSCO M, BASSI N. Isolation and characterization of biliary epithelial and stromal cells from resected human cholangiocarcinoma: A novel in vitro model to study tumor-stroma interactions. Oncology Reports 2013, 30: 1143-1148. PMID: 23807641, DOI: 10.3892/or.2013.2568.Peer-Reviewed Original ResearchMeSH KeywordsBile Duct NeoplasmsBile Ducts, IntrahepaticBiomarkers, TumorCell CommunicationCholangiocarcinomaCoculture TechniquesEpithelial-Mesenchymal TransitionFibroblastsFlow CytometryFluorescent Antibody TechniqueHumansImmunoenzyme TechniquesImmunomagnetic SeparationNeoplasm GradingStromal CellsTumor Cells, CulturedConceptsHuman biliary epithelial cellsTumor-stroma interactionsCancer-associated fibroblastsStromal cellsOrganotypic co-culture modelPrimary culturesTumor cell originMesenchymal cell markersBiliary epithelial cellsCCA cell linesRat cholangiocarcinomaCo-culture modelDevastating malignancySurgical resectionBile ductPresent studySurgical specimensDesmoplastic reactionCholangiocarcinomaCell originHuman cholangiocarcinomaCell markersFluorescent immunocytochemistryEpithelial cellsCK7
2012
Development of the bile ducts: Essentials for the clinical hepatologist
Strazzabosco M, Fabris L. Development of the bile ducts: Essentials for the clinical hepatologist. Journal Of Hepatology 2012, 56: 1159-1170. PMID: 22245898, PMCID: PMC3328609, DOI: 10.1016/j.jhep.2011.09.022.Peer-Reviewed Original ResearchConceptsLiver diseaseBile ductBiliary structuresFibropolycystic liver diseaseExtrahepatic biliary treeBiliary developmentLiver repair mechanismsHepatocellular damageBiliary treeDuctular reactionLiver repairReparative responseAlagille syndromePathogenic aspectsClinical hepatologistsCholangiopathyGrowth factorParacrine signalsEmbryonic lifeDiseaseDuctRepair mechanismsHepatologistsSyndromeTranscription factors
2008
Functional Anatomy of Normal Bile Ducts
Strazzabosco M, Fabris L. Functional Anatomy of Normal Bile Ducts. The Anatomical Record 2008, 291: 653-660. PMID: 18484611, PMCID: PMC3743051, DOI: 10.1002/ar.20664.Peer-Reviewed Original ResearchConceptsBile ductBiliary treeExtrahepatic bile ductSmall bile ductsNormal bile ductsLiver progenitor cellsBile productionBiliary epitheliumMajor ductsSecretory functionVascular structuresProgenitor cellsCholangiocyte functionFunctional anatomyBileDuctCholangiocytesIntestineFunctional interactionMorphological heterogeneityNerveGallbladderVariety of functionsEpithelium
2007
Epithelial expression of angiogenic growth factors modulate arterial vasculogenesis in human liver development
Fabris L, Cadamuro M, Libbrecht L, Raynaud P, Spirlì C, Fiorotto R, Okolicsanyi L, Lemaigre F, Strazzabosco M, Roskams T. Epithelial expression of angiogenic growth factors modulate arterial vasculogenesis in human liver development. Hepatology 2007, 47: 719-728. PMID: 18157837, DOI: 10.1002/hep.22015.Peer-Reviewed Original ResearchConceptsVascular endothelial growth factorHepatic arteryAngiogenic growth factorsBile ductAngiopoietin-1Tie-2Growth factorAngiopoietin-2VEGFR-1Endothelial cellsMural cellsCognate receptorsIntrahepatic bile ductsClose anatomical relationshipFetal human liverDifferent gestational agesEndothelial growth factorDifferent maturational stagesGestational ageHuman liver developmentImmunohistochemical expressionDuctal plateEpithelial expressionPortal vasculatureArtery