Featured Publications
The 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 vessels
2018
Integrated analysis of microRNA and mRNA expression profiles in splenomegaly induced by non-cirrhotic portal hypertension in rats
Saruwatari J, Dong C, Utsumi T, Tanaka M, McConnell M, Iwakiri Y. Integrated analysis of microRNA and mRNA expression profiles in splenomegaly induced by non-cirrhotic portal hypertension in rats. Scientific Reports 2018, 8: 17983. PMID: 30573742, PMCID: PMC6301948, DOI: 10.1038/s41598-018-36297-0.Peer-Reviewed Original ResearchConceptsCell proliferationWhole-genome microarray analysisInterferon-mediated antiviral activitySuppression of genesMicroRNA-mRNA networkSignificant differential expressionPotential biological functionsMRNA expression profilesTarget mRNAsBiological functionsExpression profilesMicroarray analysisDifferential expressionInnate immune responseMicroRNAsCellular mechanismsHematopoietic systemIntegrated analysisGenesNew insightsComprehensive profileMRNAProliferationTissue fibrosisImportant role
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 studies
2012
Intestinal and plasma VEGF levels in cirrhosis: the role of portal pressure
Huang H, Haq O, Utsumi T, Sethasine S, Abraldes JG, Groszmann RJ, Iwakiri Y. Intestinal and plasma VEGF levels in cirrhosis: the role of portal pressure. Journal Of Cellular And Molecular Medicine 2012, 16: 1125-1133. PMID: 21801303, PMCID: PMC3213314, DOI: 10.1111/j.1582-4934.2011.01399.x.Peer-Reviewed Original ResearchConceptsPlasma VEGF levelsPortal pressureVEGF levelsPortal hypertensionIntestinal VEGFDevelopment of cirrhosisFibrosis/cirrhosisAge-matched controlsGroups of ratsEnd of exposureCirrhosisRatsSignificant positive correlationWeeksHypertensionVEGFInhalationPositive correlationDifferent stagesCarbon tetrachlorideLevelsPathologyControlProteomic 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
Decreased intrahepatic response to α1‐adrenergic agonists in lipopolysaccharide‐treated rats is located in the sinusoidal area and depends on Kupffer cell function
Lee C, Loureiro‐Silva M, Abraldes JG, Iwakiri Y, Haq O, Groszmann RJ. Decreased intrahepatic response to α1‐adrenergic agonists in lipopolysaccharide‐treated rats is located in the sinusoidal area and depends on Kupffer cell function. Journal Of Gastroenterology And Hepatology 2007, 22: 893-900. PMID: 17498219, DOI: 10.1111/j.1440-1746.2007.04922.x.Peer-Reviewed Original ResearchConceptsLipopolysaccharide-treated ratsKupffer cell functionVascular responsesAdrenergic agonistsKupffer cellsNormal liverSinusoidal areaNitric oxide synthase inhibitorCell functionOxide synthase inhibitorRole of KupfferVascular tone controlNitric oxide overproductionKrebs-Henseleit solutionNitric oxide productionΑ1-adrenergic agonistDose-response curveIntrahepatic responseMicrovascular abnormalitiesSecond doseEndotoxemic ratsLiver perfusionSynthase inhibitorMethoxamineGadolinium chloride
2006
Increased phosphodiesterase-5 expression is involved in the decreased vasodilator response to nitric oxide in cirrhotic rat livers
Loureiro-Silva MR, Iwakiri Y, Abraldes JG, Haq O, Groszmann RJ. Increased phosphodiesterase-5 expression is involved in the decreased vasodilator response to nitric oxide in cirrhotic rat livers. Journal Of Hepatology 2006, 44: 886-893. PMID: 16545481, DOI: 10.1016/j.jhep.2006.01.032.Peer-Reviewed Original ResearchMeSH Keywords3',5'-Cyclic-GMP PhosphodiesterasesAnimalsCyclic Nucleotide Phosphodiesterases, Type 5Enzyme InhibitorsLiver CirculationLiver CirrhosisMaleNitric OxideNitric Oxide SynthaseOmega-N-MethylargininePhosphodiesterase InhibitorsPhosphoric Diester HydrolasesPiperazinesPurinesRatsRats, Sprague-DawleySildenafil CitrateSulfonesVasodilationConceptsPDE-5 expressionPhosphodiesterase-5 expressionCirrhotic liverCirrhotic rat liverPresence of sildenafilNitric oxideVasodilator responseDeficient responseNormal liverAscitic cirrhotic ratsDecreased vascular responseDecreased vasodilator responseConcentration-response curvesRat liverCyclic guanosine 3Second messenger cyclic guanosine 3Vasodilator effectCirrhotic ratsVascular responsesBACKGROUND/Liver perfusionDecreased responseSpontaneous NO donorSildenafil citrateNO donor
2003
A liver-specific nitric oxide donor improves the intra-hepatic vascular response to both portal blood flow increase and methoxamine in cirrhotic rats
Loureiro-Silva MR, Cadelina GW, Iwakiri Y, Groszmann RJ. A liver-specific nitric oxide donor improves the intra-hepatic vascular response to both portal blood flow increase and methoxamine in cirrhotic rats. Journal Of Hepatology 2003, 39: 940-946. PMID: 14642609, DOI: 10.1016/j.jhep.2003.09.018.Peer-Reviewed Original ResearchConceptsBlood flow increasesCirrhotic ratsPortal pressureUrsodeoxycholic acidLiver perfusionFlow/pressure curvesNO donorAscitic cirrhotic ratsBlood volume expansionBasal heart rateSitu liver perfusionNitric oxide productionNitric oxide donorDose/response curveBlood flow measurementsPortal hypertensionHemodynamic effectsArterial pressureFlow increasesVascular responsesControl ratsBlood infusionBACKGROUND/Heart rateOxide donorMesenteric vasoconstriction triggers nitric oxide overproduction in the superior mesenteric artery of portal hypertensive rats
Tsai MH, Iwakiri Y, Cadelina G, Sessa WC, Groszmann RJ. Mesenteric vasoconstriction triggers nitric oxide overproduction in the superior mesenteric artery of portal hypertensive rats. Gastroenterology 2003, 125: 1452-1461. PMID: 14598261, DOI: 10.1016/j.gastro.2003.07.014.Peer-Reviewed Original ResearchConceptsPartial portal vein ligationSuperior mesenteric arterySMA vascular resistancePortal hypertensive ratsRAL ratsMesenteric vasoconstrictionPortal pressureVascular resistanceArterial pressureHypertensive ratsMesenteric arteryNitric oxide synthase activityNitric oxide synthase enzyme activitySMA blood flowMean arterial pressurePerfusion pressure changesPortal vein ligationENOS protein expressionSham-operated ratsOxide synthase activityMonomethyl-L-arginineNitric oxide overproductionEffects of vasoconstrictionRenal artery ligationENOS catalytic activity
2002
Phosphorylation of eNOS initiates excessive NO production in early phases of portal hypertension
Iwakiri Y, Tsai MH, McCabe TJ, Gratton JP, Fulton D, Groszmann RJ, Sessa WC. Phosphorylation of eNOS initiates excessive NO production in early phases of portal hypertension. AJP Heart And Circulatory Physiology 2002, 282: h2084-h2090. PMID: 12003815, DOI: 10.1152/ajpheart.00675.2001.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic alpha-1 Receptor AgonistsAndrostadienesAnimalsEnzyme InhibitorsHypertension, PortalLigationMaleMesenteric Artery, SuperiorMethoxamineNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IIIOmega-N-MethylargininePhosphorylationPortal VeinProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktRatsRats, Sprague-DawleyVasoconstrictor AgentsWortmanninConceptsEndothelial nitric oxide synthasePortal vein ligationPhosphorylation of eNOSMesenteric arterial bedPortal hypertensionPVL groupArterial bedNO productionMale Sprague-Dawley ratsEarly portal hypertensionMonomethyl-L-arginineNitric oxide synthaseSprague-Dawley ratsExcessive NO productionG protein-coupled receptorsVivo perfusion studiesPVL ratsProtein-coupled receptorsPerfusion pressureSham groupVein ligationENOS expressionOxide synthaseReduced responsivenessKinase/Akt pathway