Featured Publications
An optimized visualization and quantitative protocol for in-depth evaluation of lymphatic vessel architecture in the liver
Jeong J, Tanaka M, Yang Y, Arefyev N, DiRito J, Tietjen G, Zhang X, McConnell M, Utsumi T, Iwakiri Y. An optimized visualization and quantitative protocol for in-depth evaluation of lymphatic vessel architecture in the liver. AJP Gastrointestinal And Liver Physiology 2023, 325: g379-g390. PMID: 37605828, PMCID: PMC10887843, DOI: 10.1152/ajpgi.00139.2023.Peer-Reviewed Original ResearchThe Sympathetic Nervous System Promotes Hepatic Lymphangiogenesis, which Is Protective Against Liver Fibrosis
Tanaka M, Jeong J, Thomas C, Zhang X, Zhang P, Saruwatari J, Kondo R, McConnell M, Utsumi T, Iwakiri Y. The Sympathetic Nervous System Promotes Hepatic Lymphangiogenesis, which Is Protective Against Liver Fibrosis. American Journal Of Pathology 2023, 193: 2182-2202. PMID: 37673329, PMCID: PMC10699132, DOI: 10.1016/j.ajpath.2023.08.004.Peer-Reviewed Original ResearchConceptsPartial portal vein ligationNoncirrhotic portal hypertensionCirrhotic patientsVascular endothelial growth factorLiver fibrosisEndothelial growth factorPortal hypertensionSympathetic denervationSympathetic nervesBDL ratsVascular diseaseIdiopathic noncirrhotic portal hypertensionGrowth factorPortal hypertensive patientsPortal vein ligationSympathetic nervous systemMechanisms of lymphangiogenesisCeliac ganglionectomyHypertensive patientsLymphatic vessel numberLiver biopsyLiver cirrhosisVein ligationPPVL ratsHepatic lymphatic vesselsSingle-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 liverEnhanced Meningeal Lymphatic Drainage Ameliorates Neuroinflammation and Hepatic Encephalopathy in Cirrhotic Rats
Hsu SJ, Zhang C, Jeong J, Lee SI, McConnell M, Utsumi T, Iwakiri Y. Enhanced Meningeal Lymphatic Drainage Ameliorates Neuroinflammation and Hepatic Encephalopathy in Cirrhotic Rats. Gastroenterology 2020, 160: 1315-1329.e13. PMID: 33227282, PMCID: PMC7956141, DOI: 10.1053/j.gastro.2020.11.036.Peer-Reviewed Original ResearchConceptsMeningeal lymphatic drainageLymphatic drainageMicroglia activationMotor functionBile duct ligation modelTumor necrosis factor αSerious neurologic complicationsMeningeal lymphatic systemNecrosis factor αDuct ligation modelNew therapeutic strategiesBrain inflammationNeurologic complicationsHepatic encephalopathyLiver cirrhosisLymph nodesRotarod testMotor dysfunctionCirrhotic ratsInterleukin-1βLigation modelInterferon γProinflammatory genesCisterna magnaTherapeutic strategies
2023
S-nitrosylation of EMMPRIN influences the migration of HSCs and MMP activity in liver fibrosis
Zhu X, Tang Z, Li W, Li X, Iwakiri Y, Liu F. S-nitrosylation of EMMPRIN influences the migration of HSCs and MMP activity in liver fibrosis. Acta Biochimica Et Biophysica Sinica 2023, 55: 1640-1649. PMID: 37700592, PMCID: PMC10577453, DOI: 10.3724/abbs.2023141.Peer-Reviewed Original ResearchConceptsExtracellular matrix metalloproteinase inducerLiver fibrosisLevels of EMMPRINMMP activitySinus epithelial cellsHSC migrationMatrix metalloproteinase inducerNormal control liversActivity of MMP2Matrix metalloproteinase activityS-nitrosylationStellate cell migrationHepatic stellate cell migrationTissue microarrayFibrotic liverFibrosisMouse liver tissueControl liversECM accumulationLiver tissueMetalloproteinase activityEMMPRIN mRNALiver areaEpithelial cellsProtein levels
2020
Endothelial Leukocyte Cell–Derived Chemotaxin 2/Tyrosine Kinase With Immunoglobulin‐Like and Epidermal Growth Factor–Like Domains 1 Signaling in Liver Fibrosis
Su T, Iwakiri Y. Endothelial Leukocyte Cell–Derived Chemotaxin 2/Tyrosine Kinase With Immunoglobulin‐Like and Epidermal Growth Factor–Like Domains 1 Signaling in Liver Fibrosis. Hepatology 2020, 72: 347-349. PMID: 32060947, DOI: 10.1002/hep.31183.Commentaries, Editorials and Letters
2019
O-GlcNAc transferase suppresses necroptosis and liver fibrosis
Zhang B, Li MD, Yin R, Liu Y, Yang Y, Mitchell-Richards KA, Nam JH, Li R, Wang L, Iwakiri Y, Chung D, Robert ME, Ehrlich BE, Bennett AM, Yu J, Nathanson MH, Yang X. O-GlcNAc transferase suppresses necroptosis and liver fibrosis. JCI Insight 2019, 4: e127709. PMID: 31672932, PMCID: PMC6948774, DOI: 10.1172/jci.insight.127709.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsFemaleHumansLiver CirrhosisMaleMiceMice, KnockoutN-AcetylglucosaminyltransferasesNecroptosisConceptsReceptor-interacting protein kinase 3Liver fibrosisLiver diseaseHepatocyte necroptosisEthanol-induced liver injuryAlcoholic liver cirrhosisChronic liver diseaseMultiple liver diseasesWeeks of ageProtein expression levelsPortal inflammationLiver cirrhosisLiver injuryBallooning degenerationElevated protein expression levelsSpontaneous genetic modelFibrosisKey suppressorKey mediatorMiceProtein kinase 3CirrhosisExpression levelsGlcNAc levelsMixed lineage kinase
2018
Is miR‐21 a potent target for liver fibrosis?
Lai S, Iwakiri Y. Is miR‐21 a potent target for liver fibrosis? Hepatology 2018, 67: 2082-2084. PMID: 29315674, PMCID: PMC5992001, DOI: 10.1002/hep.29774.Commentaries, Editorials and LettersLymphatics 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
2017
The portal hypertension syndrome: etiology, classification, relevance, and animal models
Bosch J, Iwakiri Y. The portal hypertension syndrome: etiology, classification, relevance, and animal models. Hepatology International 2017, 12: 1-10. PMID: 29064029, DOI: 10.1007/s12072-017-9827-9.BooksMeSH KeywordsAdrenergic beta-AntagonistsAnimalsAscitesCarcinoma, HepatocellularEarly Detection of CancerEsophageal and Gastric VaricesGastrointestinal HemorrhageHealthy LifestyleHemorrhageHepatic EncephalopathyHepatic VeinsHumansHypertension, PortalHypolipidemic AgentsLigationLiver CirrhosisLiver NeoplasmsModels, AnimalPrognosisSimvastatinConceptsHepatic vein pressure gradientNon-bleeding complicationsPortal hypertensionLiver transplantationDisease stagePortal hypertension syndromeAccurate risk stratificationDevelopment of varicesEndoscopic band ligationAim of treatmentPresent day therapyHealthy life styleBackgroundPortal hypertensionDecompensated patientsHVPG responseRefractory ascitesVariceal bleedingClinical decompensationLarge varicesBand ligationDay therapyHepatic encephalopathyBetter prognosisRisk stratificationEtiologic treatment
2015
Nitric oxide in liver fibrosis: The role of inducible nitric oxide synthase
Iwakiri Y. Nitric oxide in liver fibrosis: The role of inducible nitric oxide synthase. Clinical And Molecular Hepatology 2015, 21: 319-325. PMID: 26770919, PMCID: PMC4712158, DOI: 10.3350/cmh.2015.21.4.319.BooksHepatic congestion leads to fibrosis: Findings in a newly developed murine model
Hidaka H, Iwakiri Y. Hepatic congestion leads to fibrosis: Findings in a newly developed murine model. Hepatology 2015, 61: 428-430. PMID: 25283276, PMCID: PMC4303496, DOI: 10.1002/hep.27550.Commentaries, Editorials and Letters
2014
Hepatic dimethylarginine-dimethylaminohydrolase1 is reduced in cirrhosis and is a target for therapy in portal hypertension
Mookerjee RP, Mehta G, Balasubramaniyan V, Mohamed Fel Z, Davies N, Sharma V, Iwakiri Y, Jalan R. Hepatic dimethylarginine-dimethylaminohydrolase1 is reduced in cirrhosis and is a target for therapy in portal hypertension. Journal Of Hepatology 2014, 62: 325-331. PMID: 25152204, PMCID: PMC4530584, DOI: 10.1016/j.jhep.2014.08.024.Peer-Reviewed Original ResearchConceptsDDAH-1 expressionMean arterial pressurePortal hypertensionENOS activityDDAH-1Farnesoid X receptor (FXR) agonismFXR agonist obeticholic acidPortal pressure reductionAgonist obeticholic acidPortal pressure measurementsHealthy liver tissueArterial pressureENOS inhibitorHuman cirrhosisBDL ratsObeticholic acidSpecific molecular targetsPlasma ALTReceptor agonismSaline controlsCirrhosisCirrhosis ratsHypertensionOA treatmentTranslational studiesVascular pathobiology in chronic liver disease and cirrhosis – Current status and future directions
Iwakiri Y, Shah V, Rockey DC. Vascular pathobiology in chronic liver disease and cirrhosis – Current status and future directions. Journal Of Hepatology 2014, 61: 912-924. PMID: 24911462, PMCID: PMC4346093, DOI: 10.1016/j.jhep.2014.05.047.BooksConceptsChronic liver diseasePortal hypertensionLiver diseaseLiver fibrosis/cirrhosisVascular cellsMesenteric vascular circulationFibrosis/cirrhosisDynamic vascular changesCollateral vessel formationHepatic stellate cellsSinusoidal endothelial cellsGrowth factor pathwaysGrowth factor βExtrahepatic circulationExtrahepatic vasculatureArterial vasodilationLiver injuryVascular changesVasoactive peptidesHypertensionVascular pathobiologySystemic circulationStellate cellsVascular processesLiver vasculaturePathophysiology of Portal Hypertension
Iwakiri Y. Pathophysiology of Portal Hypertension. Clinics In Liver Disease 2014, 18: 281-291. PMID: 24679494, PMCID: PMC3971388, DOI: 10.1016/j.cld.2013.12.001.BooksConceptsPortal hypertensionBlood flowHyperdynamic circulatory syndromeIntrahepatic vascular resistancePortal blood flowVascular resistanceArterial vasodilationCirculatory syndromeEsophageal varicesLiver cirrhosisMajor complicationsLiver diseaseCollateral vesselsPortal circulationSystemic circulationHypertensionPathologic conditionsClinical researchCirrhosisVaricesVasodilationAscitesComplicationsPathophysiologySyndrome
2013
The lymphatic vascular system in liver diseases: its role in ascites formation
Chung C, Iwakiri Y. The lymphatic vascular system in liver diseases: its role in ascites formation. Clinical And Molecular Hepatology 2013, 19: 99-104. PMID: 23837133, PMCID: PMC3701854, DOI: 10.3350/cmh.2013.19.2.99.BooksMeSH KeywordsAscitesHumansHypertension, PortalLiver CirrhosisLiver DiseasesLiver NeoplasmsLymphangiogenesisLymphatic VesselsConceptsLiver fibrosis/cirrhosisFibrosis/cirrhosisLiver diseasePortal hypertensionAscites formationVascular systemLymphatic vascular systemNormal vascular functionPotential therapeutic targetVascular functionLiver tumorsTherapeutic targetDiseaseLymphatic systemTumor metastasisCirrhosisHypertensionLymphatic vesselsCirculatory systemPathogenesisLymphangiogenesisMetastasisTumorsLiverRoleAbsence of Nogo-B (Reticulon 4B) Facilitates Hepatic Stellate Cell Apoptosis and Diminishes Hepatic Fibrosis in Mice
Tashiro K, Satoh A, Utsumi T, Chung C, Iwakiri Y. Absence of Nogo-B (Reticulon 4B) Facilitates Hepatic Stellate Cell Apoptosis and Diminishes Hepatic Fibrosis in Mice. American Journal Of Pathology 2013, 182: 786-795. PMID: 23313137, PMCID: PMC3586693, DOI: 10.1016/j.ajpath.2012.11.032.Peer-Reviewed Original ResearchConceptsHepatic stellate cell apoptosisMF-HSCsStellate cell apoptosisHepatic fibrosisKO miceCell apoptosisHuman hepatic stellate cellsRole of NogoCarbon tetrachloride inhalationCaspase-3B knockout miceHepatic stellate cellsPotential therapeutic strategyApoptosis of HSCsWT miceFibrotic areasLiver fibrosisSelective blockadeExperimental cirrhosisLX2 cellsCirrhotic liverStellate cellsTherapeutic strategiesKnockout miceFibrosis
2011
Endothelial dysfunction in the regulation of cirrhosis and portal hypertension
Iwakiri Y. Endothelial dysfunction in the regulation of cirrhosis and portal hypertension. Liver International 2011, 32: 199-213. PMID: 21745318, PMCID: PMC3676636, DOI: 10.1111/j.1478-3231.2011.02579.x.BooksConceptsLiver sinusoidal endothelial cellsPortal hypertensionEndothelial dysfunctionArterial vasodilationPortosystemic collateral vesselsProduction of vasodilatorsDevelopment of cirrhosisCollateral vessel formationPathological vascular eventsSinusoidal endothelial cellsExtrahepatic circulationIntrahepatic resistanceOesophageal varicesVascular eventsVascular resistanceVasodilator moleculeCollateral vesselsSinusoidal microcirculationPortal veinHypertensionSystemic circulationBlood flowCirrhosisDysfunctionNitric oxideReticulon 4B (Nogo‐B) is a novel regulator of hepatic fibrosis
Zhang D, Utsumi T, Huang H, Gao L, Sangwung P, Chung C, Shibao K, Okamoto K, Yamaguchi K, Groszmann RJ, Jozsef L, Hao Z, Sessa WC, Iwakiri Y. Reticulon 4B (Nogo‐B) is a novel regulator of hepatic fibrosis. Hepatology 2011, 53: 1306-1315. PMID: 21480333, PMCID: PMC3667398, DOI: 10.1002/hep.24200.Peer-Reviewed Original ResearchConceptsBile duct ligationLiver fibrosisPortal pressureKO micePortal hypertensionReticulon 4BWT mice 4 weeksMice 4 weeksFibrosis/cirrhosisSham-operated controlsB knockout miceHepatic stellate cellsPotential therapeutic targetHuman liver sectionsAbsence of NogoGrowth factor β stimulationMechanism of NogoTGFβ/SMAD2WT miceVascular injuryHepatic fibrosisSham operationCirrhotic liverDuct ligationStellate cells
2008
Vascular biology and pathobiology of the liver: Report of a single‐topic symposium
Iwakiri Y, Grisham M, Shah V. Vascular biology and pathobiology of the liver: Report of a single‐topic symposium. Hepatology 2008, 47: 1754-1763. PMID: 18393322, PMCID: PMC2724750, DOI: 10.1002/hep.22203.BooksConceptsPortal hypertensionVascular biologyIschemia-reperfusion injurySingle Topic ConferenceMajority of morbidityClinical sequelaeIR injurySpecific disease syndromesLiver diseaseVascular syndromesVascular diseaseVascular cell signalingHypertensionDisease syndromeLiver cellsSyndromeMajor vascular defectsLiverVascular defectsInjuryDiseasePathobiologyAmerican AssociationCell signalingCirrhosis