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 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 liver
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 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
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.Books
2013
Reticulon 4B (Nogo‐B) facilitates hepatocyte proliferation and liver regeneration in mice
Gao L, Utsumi T, Tashiro K, Liu B, Zhang D, Swenson ES, Iwakiri Y. Reticulon 4B (Nogo‐B) facilitates hepatocyte proliferation and liver regeneration in mice. Hepatology 2013, 57: 1992-2003. PMID: 23299899, PMCID: PMC3628958, DOI: 10.1002/hep.26235.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell ProliferationEpidermal Growth FactorHepatectomyHepatocyte Growth FactorHepatocytesInterleukin-6LiverLiver RegenerationMaleMiceMice, Inbred C57BLMice, KnockoutModels, AnimalMyelin ProteinsNogo ProteinsSignal TransductionSTAT3 Transcription FactorTime FactorsTransforming Growth Factor betaConceptsHepatocyte growth factorRole of NogoInterleukin-6Hepatocyte proliferationLiver regenerationEpidermal growth factorReticulon 4BTGF-β1Growth factorKi67 labeling indexB knockout miceHepatic stellate cellsReal-time polymerase chain reactionQuantitative real-time polymerase chain reactionIL-6/signal transducerGrowth factor βTime-dependent mannerRemnant liverKO miceLiver fibrosisPolymerase chain reactionInhibitor of DNAStellate cellsKnockout miceLabeling indexAbsence 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
Reticulon 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