Featured Publications
Liver injury in COVID-19 and IL-6 trans-signaling-induced endotheliopathy
McConnell MJ, Kawaguchi N, Kondo R, Sonzogni A, Licini L, Valle C, Bonaffini PA, Sironi S, Alessio MG, Previtali G, Seghezzi M, Zhang X, Lee A, Pine AB, Chun HJ, Zhang X, Fernandez-Hernando C, Qing H, Wang A, Price C, Sun Z, Utsumi T, Hwa J, Strazzabosco M, Iwakiri Y. Liver injury in COVID-19 and IL-6 trans-signaling-induced endotheliopathy. Journal Of Hepatology 2021, 75: 647-658. PMID: 33991637, PMCID: PMC8285256, DOI: 10.1016/j.jhep.2021.04.050.Peer-Reviewed Original ResearchConceptsLiver sinusoidal endothelial cellsLiver injuryInterleukin-6Sinusoidal endothelial cellsAlanine aminotransferaseLiver histologyD-dimerCOVID-19Primary human liver sinusoidal endothelial cellsSARS-CoV-2 infectionHuman liver sinusoidal endothelial cellsEndothelial cellsSoluble glycoprotein 130IL-6 levelsSmall-interfering RNA knockdownJAK inhibitor ruxolitinibFactor VIII activityProinflammatory factorsInflammatory signalsLarge cohortInhibitor ruxolitinibVWF antigenEndotheliopathyPatientsInjury
2015
Nonalcoholic 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 vasculaturePigment Epithelium-Derived Factor (PEDF) Suppresses IL-1β-Mediated c-Jun N-Terminal Kinase (JNK) Activation to Improve Hepatocyte Insulin Signaling
Gattu AK, Birkenfeld AL, Iwakiri Y, Jay S, Saltzman M, Doll J, Protiva P, Samuel VT, Crawford SE, Chung C. Pigment Epithelium-Derived Factor (PEDF) Suppresses IL-1β-Mediated c-Jun N-Terminal Kinase (JNK) Activation to Improve Hepatocyte Insulin Signaling. Endocrinology 2014, 155: 1373-1385. PMID: 24456163, PMCID: PMC5393334, DOI: 10.1210/en.2013-1785.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAnimalsEye ProteinsGene Expression RegulationGlucose Tolerance TestHepatocytesHumansInflammationInsulinInsulin ResistanceInterleukin-1betaJNK Mitogen-Activated Protein KinasesLiverMaleMetabolic SyndromeMetabolomicsMiceMice, Inbred C57BLMice, KnockoutMicrospheresNerve Growth FactorsObesityPalmitic AcidPhenotypeRNA InterferenceSerpinsSignal TransductionSuccinic AcidConceptsPigment epithelium-derived factorKO miceMetabolic syndromeIL-1βC-Jun N-terminal kinase (JNK) activationElevated pigment epithelium-derived factorIL-1β challengeHuman hepatocytesIL-1β expressionHuman metabolic syndromeEpithelium-derived factorPEDF-knockout miceInflammatory markersGlucose intoleranceSerum levelsC-Jun N-terminal kinaseKinase activationAntiinflammatory proteinHepatic insulinKnockout micePigment epitheliumN-terminal kinaseMiceSyndromeMetabolic homeostasis
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 index
2011
S-nitrosylation of proteins: A new insight into endothelial cell function regulated by eNOS-derived NO
Iwakiri Y. S-nitrosylation of proteins: A new insight into endothelial cell function regulated by eNOS-derived NO. Nitric Oxide 2011, 25: 95-101. PMID: 21554971, PMCID: PMC3152628, DOI: 10.1016/j.niox.2011.04.014.BooksConceptsS-nitrosylationCellular processesGolgi apparatusIntracellular membrane domainPlasma membrane caveolaeEndothelial cell functionCell functionProtein traffickingMembrane caveolaeMembrane domainsCytoplasmic faceTarget proteinsCell cycleSignaling mechanismMessenger moleculesCell growthRedox stateProteinNitric oxide synthaseIntracellular reactionsNew insightsEndothelial NOSNitric oxideEndothelial nitric oxide synthaseFamily members