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
2019
Digoxin improves steatohepatitis with differential involvement of liver cell subsets in mice through inhibition of PKM2 transactivation
Zhao P, Han SN, Arumugam S, Yousaf MN, Qin Y, Jiang JX, Torok NJ, Chen Y, Mankash MS, Liu J, Li J, Iwakiri Y, Ouyang X. Digoxin improves steatohepatitis with differential involvement of liver cell subsets in mice through inhibition of PKM2 transactivation. AJP Gastrointestinal And Liver Physiology 2019, 317: g387-g397. PMID: 31411894, PMCID: PMC6842989, DOI: 10.1152/ajpgi.00054.2019.Peer-Reviewed Original ResearchConceptsHigh-fat dietSignificant clinical applicabilityHuman nonalcoholic steatohepatitisNonalcoholic steatohepatitisOral digoxinLiver injuryCell subsetsPathway activationMouse modelHigh-fat diet mouse modelLiver injury mouse modelHepatocyte mitochondrial dysfunctionClinical applicabilityDiet mouse modelInjury mouse modelDifferential involvementLarge clinical experienceNLRP3 inflammasome activationSignificant protective effectHIF-1α transactivationHepatic oxidative stress responseHypoxia-inducible factorLiver inflammationHFD miceWide dosage range
2017
Alcohol and calcium make a potent cocktail
Iwakiri Y, Nathanson MH. Alcohol and calcium make a potent cocktail. The Journal Of Physiology 2017, 595: 3109-3110. PMID: 28295353, PMCID: PMC5430223, DOI: 10.1113/jp274133.Commentaries, Editorials and Letters
2016
Cellular distribution of injected PLGA-nanoparticles in the liver
Park JK, Utsumi T, Seo YE, Deng Y, Satoh A, Saltzman WM, Iwakiri Y. Cellular distribution of injected PLGA-nanoparticles in the liver. Nanomedicine Nanotechnology Biology And Medicine 2016, 12: 1365-1374. PMID: 26961463, PMCID: PMC4889500, DOI: 10.1016/j.nano.2016.01.013.Peer-Reviewed Original ResearchConceptsPLGA nanoparticlesSafety of nanoparticlesUptake of nanoparticlesNanoparticle deliveryLiver sinusoidal endothelial cellsNanoparticle retentionNanoparticlesHepatic stellate cellsSinusoidal endothelial cellsKupffer cellsStellate cellsEndothelial cellsTarget cell typeCell typesClodronate liposomesLiver therapyLiver cellsMajor cellsLiverCell populationsCellular distributionLiposomesCellsHepatocytes
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
Pigment 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