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
The 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 profilesInflammation
2020
Reduced Nogo expression inhibits diet-induced metabolic disorders by regulating ChREBP and insulin activity
Zhang S, Guo F, Yu M, Yang X, Yao Z, Li Q, Wei Z, Feng K, Zeng P, Zhao D, Li X, Zhu Y, Miao QR, Iwakiri Y, Chen Y, Han J, Duan Y. Reduced Nogo expression inhibits diet-induced metabolic disorders by regulating ChREBP and insulin activity. Journal Of Hepatology 2020, 73: 1482-1495. PMID: 32738448, DOI: 10.1016/j.jhep.2020.07.034.Peer-Reviewed Original ResearchConceptsDiet-induced metabolic disordersHepatic lipid accumulationInsulin sensitivityMetabolic disordersInsulin resistanceNogo expressionNon-alcoholic fatty liver diseaseDiet-induced body weight gainInsulin activityDiet-induced glucose intoleranceLipid accumulationFatty liver diseaseHigh-fructose dietGrowth factor 21Littermate control miceDe novo lipogenesisHigh-carbohydrate dietBody weight gainCarbohydrate-responsive element-binding proteinExpression of ChREBPChREBP activityEndoplasmic reticulum stressMetabolic complicationsGlucose intoleranceLiver disease
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 ResearchConceptsReceptor-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
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
2017
Biology of portal hypertension
McConnell M, Iwakiri Y. Biology of portal hypertension. Hepatology International 2017, 12: 11-23. PMID: 29075990, PMCID: PMC7090883, DOI: 10.1007/s12072-017-9826-x.BooksMeSH KeywordsAnimalsAscitesBlood PlateletsEndothelial CellsEsophageal and Gastric VaricesFibrosisGastrointestinal HemorrhageHepatic EncephalopathyHepatic Veno-Occlusive DiseaseHepatorenal SyndromeHumansHypertension, PortalLiverMiceMicrovesselsModels, AnimalNeovascularization, PathologicRenal InsufficiencySplanchnic CirculationThrombosisVascular ResistanceConceptsLiver sinusoidal endothelial cellsPortal hypertensionMicrovascular thrombosisHepatic stellate cell activationHyperdynamic circulatory syndromeSystemic arterial vasodilationChronic liver diseaseIntrahepatic vascular resistanceSinusoidal portal hypertensionPortal hypertension resultsStellate cell activationSinusoidal endothelial cellsVascular biology researchHepatorenal syndromeGastroesophageal varicesVariceal hemorrhageVascular resistanceArterial vasodilationCirculatory syndromeRenal failureHepatic encephalopathyHypertension resultsLiver diseasePortosystemic shuntMesenteric vasculatureAn endoplasmic reticulum protein, Nogo‐B, facilitates alcoholic liver disease through regulation of kupffer cell polarization
Park J, Shao M, Kim MY, Baik SK, Cho MY, Utsumi T, Satoh A, Ouyang X, Chung C, Iwakiri Y. An endoplasmic reticulum protein, Nogo‐B, facilitates alcoholic liver disease through regulation of kupffer cell polarization. Hepatology 2017, 65: 1720-1734. PMID: 28090670, PMCID: PMC5397326, DOI: 10.1002/hep.29051.Peer-Reviewed Original ResearchConceptsAlcoholic liver diseasePositive Kupffer cellsKupffer cellsLiver injuryALD patientsLiver diseaseM1 polarizationKO miceM2 polarizationLieber-DeCarli ethanol liquid dietDisease severityM1/M2 polarizationKupffer cell polarizationEthanol liquid dietHepatic triglyceride levelsM2 macrophage polarizationHigher hepatic triglyceride levelsChronic ethanol feedingNew therapeutic targetsER stressAbsence of NogoM2 statusWT miceM1 activationTriglyceride levels
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 roleNonalcoholic fatty liver disease induced by noncanonical Wnt and its rescue by Wnt3a
Wang S, Song K, Srivastava R, Dong C, Go G, Li N, Iwakiri Y, Mani A. Nonalcoholic fatty liver disease induced by noncanonical Wnt and its rescue by Wnt3a. The FASEB Journal 2015, 29: 3436-3445. PMID: 25917329, PMCID: PMC4511193, DOI: 10.1096/fj.15-271171.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsCell Line, TumorCell TransdifferentiationFatty LiverHep G2 CellsHepatocytesHumansLiverLow Density Lipoprotein Receptor-Related Protein-6MiceMice, Inbred C57BLNon-alcoholic Fatty Liver DiseaseProtein BindingProtein Kinase CProtein Kinase C-alphaRho-Associated KinasesSignal TransductionTransforming Growth Factor beta1VimentinWnt Signaling PathwayWnt3A ProteinConceptsNonalcoholic fatty liver diseaseFatty liver diseaseNonalcoholic steatohepatitisLiver diseaseLDL receptor-related protein 6NASH-related liver diseaseMetabolic risk factorsChronic liver diseaseEarly-onset atherosclerosisImportant potential therapeutic targetTGF-β1 activityPotential therapeutic targetDisease pathwaysRas homolog family member ASmooth muscle αFamily member ARisk factorsDisease progressionCommon causeLRP6 knockdownTherapeutic targetWnt3a administrationHepatocyte transdifferentiationDiseaseMuscle α
2014
Vascular 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 researchCirrhosisVaricesVasodilationAscitesComplicationsPathophysiologySyndromePathophysiology of Portal Hypertension
Iwakiri Y, Groszmann R. Pathophysiology of Portal Hypertension. 2014, 3-14. DOI: 10.1007/978-1-4939-0002-2_1.Peer-Reviewed Original ResearchPortal hypertensionLiver diseaseHyperdynamic splanchnic circulationHepatic vascular resistanceSerious liver diseaseExtrahepatic diseaseGastroesophageal varicesVascular resistanceHemodynamic abnormalitiesSplanchnic circulationLethal complicationCirculatory derangementsHypertensionDiseaseCurrent knowledgeVaricesAscitesComplicationsHemorrhageDerangementPathophysiologyRegulatory mechanismsAbnormalitiesFunctional aspects
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.BooksConceptsLiver fibrosis/cirrhosisFibrosis/cirrhosisLiver diseasePortal hypertensionAscites formationVascular systemLymphatic vascular systemNormal vascular functionPotential therapeutic targetVascular functionLiver tumorsTherapeutic targetDiseaseLymphatic systemTumor metastasisCirrhosisHypertensionLymphatic vesselsCirculatory systemPathogenesisLymphangiogenesisMetastasisTumorsLiverRole
2010
The Systemic and Splanchnic Circulations
Iwakiri Y. The Systemic and Splanchnic Circulations. Clinical Gastroenterology 2010, 305-321. DOI: 10.1007/978-1-60761-866-9_15.Peer-Reviewed Original ResearchPortal hypertensionArterial vasodilatationSplanchnic circulationSystemic circulationNitric oxideInitiation of vasodilatationSystemic hemodynamic abnormalitiesDevelopment of complicationsSplanchnic blood flowProgressive vasodilatationHemodynamic abnormalitiesIntestinal microcirculationLiver cirrhosisLiver diseaseVasodilator moleculeHypertensionVasodilatationBlood flowCirrhosisPatientsMolecular mechanismsKey eventsSensory mechanismsCirculationComplications
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
2006
The hyperdynamic circulation of chronic liver diseases: From the patient to the molecule
Iwakiri Y, Groszmann RJ. The hyperdynamic circulation of chronic liver diseases: From the patient to the molecule. Hepatology 2006, 43: s121-s131. PMID: 16447289, DOI: 10.1002/hep.20993.BooksMeSH KeywordsAdrenomedullinAnimalsBiological FactorsBlood PressureCannabinoid Receptor ModulatorsCarbon MonoxideChronic DiseaseDisease Models, AnimalEndothelium, VascularHumansHydrogen SulfideHypertension, PortalLiverLiver DiseasesNitric OxidePeptidesSplanchnic CirculationTumor Necrosis Factor-alphaVasodilationConceptsHyperdynamic circulatory syndromeChronic liver diseaseCirculatory syndromeLiver diseaseVasodilator moleculeClinical observationsExperimental modelComplex pathophysiological mechanismsHyperdynamic circulationProgressive vasodilatationPortal hypertensionPathophysiological mechanismsVascular abnormalitiesComplex syndromeMultiple organsPatientsNitric oxideSyndromeVasodilatationDiseaseDetrimental effectsHypertensionAbnormalitiesComplex mechanisms
2004
The paradox: vasoconstriction and vasodilation
Iwakiri Y, Groszmann R. The paradox: vasoconstriction and vasodilation. 2004, 57-67. DOI: 10.1007/978-94-007-1042-9_7.Peer-Reviewed Original ResearchPortal hypertensionLiver diseaseVascular toneNitric oxideHyperdynamic circulatory syndromeChronic liver diseaseHomeostatic mechanismsBody's homeostatic mechanismsCirculatory syndromeImpaired oxygenationElectrolyte imbalanceHomeostatic functionsKey moleculesHypertensionProgressive alterationDiseaseToneVasoconstrictionVasodilationPatientsPatients1Major rolePathogenesisSyndromeAbnormalities