Featured Publications
Interleukin-7-based identification of liver lymphatic endothelial cells reveals their unique structural features
Yang Y, Jeong J, Su T, Lai S, Zhang P, Garcia-Milian R, Graham M, Liu X, McConnell M, Utsumi T, Pereira J, Iwakiri Y. Interleukin-7-based identification of liver lymphatic endothelial cells reveals their unique structural features. JHEP Reports 2024, 6: 101069. PMID: 38966234, PMCID: PMC11222939, DOI: 10.1016/j.jhepr.2024.101069.Peer-Reviewed Original ResearchCell surface structuresLymphatic endothelial cellsPublished single-cell RNA-sequencingRNA-seq analysisScRNA-seq analysisSingle-cell RNA sequencingLymphatic systemEndothelial cellsInterleukin-7RNA-seqScRNA-seqExpressed genesRNA sequencingTranscriptomic changesLow abundanceI/R liver injuryGenesIsolation protocolLiver cell typesCell typesIsolation methodLiver of miceHuman liver specimensHeterozygous miceMouse liverThe evolving role of liver sinusoidal endothelial cells in liver health and disease
McConnell M, Kostallari E, Ibrahim S, Iwakiri Y. The evolving role of liver sinusoidal endothelial cells in liver health and disease. Hepatology 2023, 78: 649-669. PMID: 36626620, PMCID: PMC10315420, DOI: 10.1097/hep.0000000000000207.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsLiver diseaseAlcohol-associated liver diseaseEndothelial cellsLiver transplant rejectionIschemia-reperfusion injuryLiver sinusoidal endothelial cellsSinusoidal endothelial cellsPortal hypertensionLiver inflammationMicrovascular thrombosisViral hepatitisReperfusion injuryTransplant rejectionLiver healthLiver pathologyLiver homeostasisLiver regenerationQuiescent phenotypePathological processesUnique populationDiseaseLSECLiver biologyGene expression profilesInflammationLiver injury in COVID-19 and IL-6 trans-signaling-induced endotheliopathy
McConnell MJ, Kawaguchi N, Kondo R, Sonzogni A, Licini L, Valle C, Bonaffini PA, Sironi S, Alessio MG, Previtali G, Seghezzi M, Zhang X, Lee A, Pine AB, Chun HJ, Zhang X, Fernandez-Hernando C, Qing H, Wang A, Price C, Sun Z, Utsumi T, Hwa J, Strazzabosco M, Iwakiri Y. Liver injury in COVID-19 and IL-6 trans-signaling-induced endotheliopathy. Journal Of Hepatology 2021, 75: 647-658. PMID: 33991637, PMCID: PMC8285256, DOI: 10.1016/j.jhep.2021.04.050.Peer-Reviewed Original ResearchConceptsLiver sinusoidal endothelial cellsLiver injuryInterleukin-6Sinusoidal endothelial cellsAlanine aminotransferaseLiver histologyD-dimerCOVID-19Primary human liver sinusoidal endothelial cellsSARS-CoV-2 infectionHuman liver sinusoidal endothelial cellsEndothelial cellsSoluble glycoprotein 130IL-6 levelsSmall-interfering RNA knockdownJAK inhibitor ruxolitinibFactor VIII activityProinflammatory factorsInflammatory signalsLarge cohortInhibitor ruxolitinibVWF antigenEndotheliopathyPatientsInjurySingle-Cell Transcriptomics Reveals Zone-Specific Alterations of Liver Sinusoidal Endothelial Cells in Cirrhosis
Su T, Yang Y, Lai S, Jeong J, Jung Y, McConnell M, Utsumi T, Iwakiri Y. Single-Cell Transcriptomics Reveals Zone-Specific Alterations of Liver Sinusoidal Endothelial Cells in Cirrhosis. Cellular And Molecular Gastroenterology And Hepatology 2020, 11: 1139-1161. PMID: 33340713, PMCID: PMC7903131, DOI: 10.1016/j.jcmgh.2020.12.007.Peer-Reviewed Original ResearchConceptsLiver sinusoidal endothelial cellsCirrhotic miceSinusoidal endothelial cellsLiver cirrhosisEndothelial cellsIntrahepatic vascular resistanceCarbon tetrachloride inhalationNovel therapeutic strategiesNitric oxide productionCirrhotic mouse liverEC populationsVascular resistanceClinical complicationsLiver fibrosisTherapeutic strategiesCirrhosisOxide productionEndocytic receptorMiceAbstractTextZone 3Extracellular matrix genesVascular ECsLymphatic ECsMouse liver
2024
Chapter 13 Liver Sinusoidal Cells in alcohol-associated liver disease
Iwakiri Y. Chapter 13 Liver Sinusoidal Cells in alcohol-associated liver disease. 2024, 285-291. DOI: 10.1016/b978-0-323-95262-0.00013-9.Peer-Reviewed Original ResearchAlcohol-associated liver diseaseLiver sinusoidal endothelial cellsPathogenesis of alcohol-associated liver diseaseChronic alcohol consumptionSinusoidal endothelial cellsLiver diseaseNormal function of immune cellsEndothelial cellsFunction of immune cellsSinusoidal cellsAlcohol consumptionIntrahepatic vascular toneHepatic stellate cellsEndothelial cell populationLiver sinusoidal cellsLiver cell typesImmune cellsAntigen clearanceVascular toneKupffer cells/macrophagesKupffer cellsStellate cellsCell populationsLiver homeostasisLiver
2023
Endotheliopathy of liver sinusoidal endothelial cells in liver disease
Kondo R, Iwakiri Y, Kage M, Yano H. Endotheliopathy of liver sinusoidal endothelial cells in liver disease. Pathology International 2023, 73: 381-393. PMID: 37589433, DOI: 10.1111/pin.13361.Peer-Reviewed Original ResearchConceptsLiver diseaseSinusoidal endothelial cellsEndothelial cellsLiver injuryLiver tissueIntercellular adhesion molecule-1Improvement of thrombocytopeniaNeutrophil chemotactic mediatorsChronic hepatitis CLiver sinusoidal endothelial cellsSetting of inflammationSevere hepatic inflammationAdhesion molecule-1Largest solid organPotential therapeutic strategyVascular endothelial cellsVon Willebrand factorHepatitis CNeutrophil accumulationHepatic inflammationChemotactic mediatorsIL-6Antithrombotic factorsChemokine ligandSolid organs
2021
Pathological characteristics of liver sinusoidal thrombosis in COVID‐19 patients: A series of 43 cases
Kondo R, Kawaguchi N, McConnell MJ, Sonzogni A, Licini L, Valle C, Bonaffini PA, Sironi S, Alessio MG, Previtali G, Seghezzi M, Zhang X, Sun Z, Utsumi T, Strazzabosco M, Iwakiri Y. Pathological characteristics of liver sinusoidal thrombosis in COVID‐19 patients: A series of 43 cases. Hepatology Research 2021, 51: 1000-1006. PMID: 34260803, PMCID: PMC8444906, DOI: 10.1111/hepr.13696.Peer-Reviewed Original ResearchCOVID-19 patientsVon Willebrand factorLiver injuryPatient's liverPapa Giovanni XXIII HospitalHigher serum ALTLiver sinusoidal endothelial cellsLiver biopsy samplesSinusoidal endothelial cellsSinusoidal thrombosisSerum ALTAST levelsPathological characteristicsHigher fibrinogenPlatelet microthrombiBiopsy samplesMultiple organsPatientsDisease severityCoronavirus diseaseLiverEndothelial cellsInjurySecondary damageWillebrand factorPortal hypertension in cirrhosis: Pathophysiological mechanisms and therapy
Iwakiri Y, Trebicka J. Portal hypertension in cirrhosis: Pathophysiological mechanisms and therapy. JHEP Reports 2021, 3: 100316. PMID: 34337369, PMCID: PMC8318926, DOI: 10.1016/j.jhepr.2021.100316.Peer-Reviewed Original ResearchLiver sinusoidal endothelial cellsHepatic stellate cellsPortal hypertensionChronic liver diseaseIntrahepatic vascular resistanceSinusoidal endothelial cellsExtrahepatic vasculatureVascular resistanceMicrovascular thrombosisHaemodynamic changesLiver diseasePathophysiological mechanismsPortal veinHypertensionPreclinical studiesEffective treatmentStellate cellsPathogenic complexityExtrahepatic mechanismsClinical advancesEffective therapeuticsUnsuccessful translationEndothelial cellsCirrhosisDysregulation
2018
Lymphatics in the liver
Tanaka M, Iwakiri Y. Lymphatics in the liver. Current Opinion In Immunology 2018, 53: 137-142. PMID: 29772409, PMCID: PMC6986420, DOI: 10.1016/j.coi.2018.04.028.BooksConceptsHepatic lymphatic systemLymphatic systemViral hepatitisLiver diseaseLarge lymphHepatic lymphatic vesselsDiseased liverHepatocellular carcinomaLymphatic endothelial cellsEndothelial cellsLiverLymphatic vesselsPotential roleSignificant increaseDiseaseCurrent knowledgeReview articleOrgansCirrhosisHepatitisLymphCarcinomaLymphatics
2016
The Hepatic Lymphatic Vascular System: Structure, Function, Markers, and Lymphangiogenesis
Tanaka M, Iwakiri Y. The Hepatic Lymphatic Vascular System: Structure, Function, Markers, and Lymphangiogenesis. Cellular And Molecular Gastroenterology And Hepatology 2016, 2: 733-749. PMID: 28105461, PMCID: PMC5240041, DOI: 10.1016/j.jcmgh.2016.09.002.BooksVascular systemLymphatic vascular systemLymphatic vessel dysfunctionTransgenic animal modelsLiver lymphaticsVessel dysfunctionAnimal modelsStudy of lymphaticsFluid homeostasisLymphatic endothelial cellsEndothelial cellsSpecific markersVascular researchTissue fluid homeostasisLymphaticsMarkersCurrent knowledgeCell isolationLymphangiogenesisDysfunctionPathogenesisDiseaseLiverCellular distribution of injected PLGA-nanoparticles in the liver
Park JK, Utsumi T, Seo YE, Deng Y, Satoh A, Saltzman WM, Iwakiri Y. Cellular distribution of injected PLGA-nanoparticles in the liver. Nanomedicine Nanotechnology Biology And Medicine 2016, 12: 1365-1374. PMID: 26961463, PMCID: PMC4889500, DOI: 10.1016/j.nano.2016.01.013.Peer-Reviewed Original ResearchConceptsPLGA nanoparticlesSafety of nanoparticlesUptake of nanoparticlesNanoparticle deliveryLiver sinusoidal endothelial cellsNanoparticle retentionNanoparticlesHepatic stellate cellsSinusoidal endothelial cellsKupffer cellsStellate cellsEndothelial cellsTarget cell typeCell typesClodronate liposomesLiver therapyLiver cellsMajor cellsLiverCell populationsCellular distributionLiposomesCellsHepatocytes
2015
Nitric oxide in liver diseases
Iwakiri Y, Kim MY. Nitric oxide in liver diseases. Trends In Pharmacological Sciences 2015, 36: 524-536. PMID: 26027855, PMCID: PMC4532625, DOI: 10.1016/j.tips.2015.05.001.BooksConceptsLiver sinusoidal endothelial cellsEndothelial NO synthaseLiver diseaseNitric oxideSinusoidal endothelial cellsInducible NOSNO synthaseEndothelial cellsPathological processesDiseaseDisease developmentLiverFatty acidsS-guanylationComplicated rolePathophysiologyPathogenesisNOSProgressionImportant role
2012
Proteomic Identification of S-Nitrosylated Golgi Proteins: New Insights into Endothelial Cell Regulation by eNOS-Derived NO
Sangwung P, Greco TM, Wang Y, Ischiropoulos H, Sessa WC, Iwakiri Y. Proteomic Identification of S-Nitrosylated Golgi Proteins: New Insights into Endothelial Cell Regulation by eNOS-Derived NO. PLOS ONE 2012, 7: e31564. PMID: 22363674, PMCID: PMC3283662, DOI: 10.1371/journal.pone.0031564.Peer-Reviewed Original ResearchConceptsGolgi proteinsGolgi phosphoprotein 3S-nitrosylationGolgi apparatusCysteine residuesSelective S-nitrosylationPlasma membrane caveolaeGolgi/endoplasmic reticulumProtein S-nitrosylationTarget cysteine residuesEndothelial cellsEndothelial nitric oxide synthaseMembrane caveolaeEndothelial cell lysatesProteomic identificationEndothelial cell regulationGolgi membranesBiotin switchCell regulationEndoplasmic reticulumENOS stimulationCell lysatesProteinImmunoprecipitationWestern blot
2007
Loss of Akt1 Leads to Severe Atherosclerosis and Occlusive Coronary Artery Disease
Fernández-Hernando C, Ackah E, Yu J, Suárez Y, Murata T, Iwakiri Y, Prendergast J, Miao RQ, Birnbaum MJ, Sessa WC. Loss of Akt1 Leads to Severe Atherosclerosis and Occlusive Coronary Artery Disease. Cell Metabolism 2007, 6: 446-457. PMID: 18054314, PMCID: PMC3621848, DOI: 10.1016/j.cmet.2007.10.007.Peer-Reviewed Original ResearchMeSH KeywordsAcute Coronary SyndromeAnimalsApolipoproteins EApoptosisAtherosclerosisBone Marrow TransplantationCoronary OcclusionDisease Models, AnimalEndothelial CellsFemaleHumansInflammation MediatorsMacrophagesMaleMiceMice, KnockoutNitric Oxide Synthase Type IINitric Oxide Synthase Type IIIProto-Oncogene Proteins c-aktConceptsLoss of Akt1Apolipoprotein E knockout backgroundOcclusive coronary artery diseaseBone marrow transfer experimentsAcute coronary syndromeCoronary artery diseaseLesion expansionCoronary syndromeCoronary atherosclerosisSevere atherosclerosisArtery diseaseInflammatory mediatorsCoronary lesionsVascular protectionVascular originProinflammatory genesENOS phosphorylationCardiovascular systemLesion formationGenetic ablationEndothelial cellsAtherogenesisEnhanced expressionKnockout backgroundVessel wallVascular endothelial dysfunction in cirrhosis
Iwakiri Y, Groszmann RJ. Vascular endothelial dysfunction in cirrhosis. Journal Of Hepatology 2007, 46: 927-934. PMID: 17391799, DOI: 10.1016/j.jhep.2007.02.006.BooksConceptsEndothelium-dependent relaxationEndothelial dysfunctionSinusoidal endothelial cellsPortal hypertensionVascular nitric oxide levelsVascular endothelial dysfunctionNitric oxide levelsSEC dysfunctionVascular resistanceEarly key eventSplanchnic circulationLiver cirrhosisVasodilator moleculeLiver microcirculationSystemic circulationOxide levelsCirrhosisDysfunctionEndothelial cellsHypertensionMultiple diseasesKey eventsArteryMicrocirculationDisease