2023
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 vesselsAn 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 Research
2021
Alcohol-induced Hsp90 acetylation is a novel driver of liver sinusoidal endothelial dysfunction and alcohol-related liver disease
Yang Y, Sangwung P, Kondo R, Jung Y, McConnell MJ, Jeong J, Utsumi T, Sessa WC, Iwakiri Y. Alcohol-induced Hsp90 acetylation is a novel driver of liver sinusoidal endothelial dysfunction and alcohol-related liver disease. Journal Of Hepatology 2021, 75: 377-386. PMID: 33675874, PMCID: PMC8292196, DOI: 10.1016/j.jhep.2021.02.028.Peer-Reviewed Original ResearchConceptsEndothelial nitric oxide synthaseAlcohol-induced liver injuryLiver sinusoidal endothelial cellsAlcohol-related liver diseaseLiver injuryLSEC dysfunctionHsp90 acetylationNO productionHistone deacetylase 6Liver diseaseTherapeutic strategiesHeat shock protein 90 (Hsp90) acetylationLiver sinusoidal endothelial dysfunctionSinusoidal endothelial cell dysfunctionMouse liver sinusoidal endothelial cellsEndothelial cell dysfunctionNitric oxide synthaseEthanol-fed miceSinusoidal endothelial dysfunctionPotential therapeutic approachPotential therapeutic strategyNitric oxide productionNew therapeutic strategiesSinusoidal endothelial cellsAcetylation of Hsp90
2020
Single-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
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
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 vasculature