2017
An endoplasmic reticulum protein, Nogo‐B, facilitates alcoholic liver disease through regulation of kupffer cell polarization
Park J, Shao M, Kim MY, Baik SK, Cho MY, Utsumi T, Satoh A, Ouyang X, Chung C, Iwakiri Y. An endoplasmic reticulum protein, Nogo‐B, facilitates alcoholic liver disease through regulation of kupffer cell polarization. Hepatology 2017, 65: 1720-1734. PMID: 28090670, PMCID: PMC5397326, DOI: 10.1002/hep.29051.Peer-Reviewed Original ResearchConceptsAlcoholic liver diseasePositive Kupffer cellsKupffer cellsLiver injuryALD patientsLiver diseaseM1 polarizationKO miceM2 polarizationLieber-DeCarli ethanol liquid dietDisease severityM1/M2 polarizationKupffer cell polarizationEthanol liquid dietHepatic triglyceride levelsM2 macrophage polarizationHigher hepatic triglyceride levelsChronic ethanol feedingNew therapeutic targetsER stressAbsence of NogoM2 statusWT miceM1 activationTriglyceride levels
2015
Pigment Epithelium-Derived Factor (PEDF) Inhibits Wnt/β-catenin Signaling in the Liver
Protiva P, Gong J, Sreekumar B, Torres R, Zhang X, Belinsky GS, Cornwell M, Crawford SE, Iwakiri Y, Chung C. Pigment Epithelium-Derived Factor (PEDF) Inhibits Wnt/β-catenin Signaling in the Liver. Cellular And Molecular Gastroenterology And Hepatology 2015, 1: 535-549.e14. PMID: 26473164, PMCID: PMC4604042, DOI: 10.1016/j.jcmgh.2015.06.006.Peer-Reviewed Original ResearchLow-density lipoprotein receptor-related protein 6Catenin signalingWnt coreceptor low-density lipoprotein receptor-related protein 6KO liversLipoprotein receptor-related protein 6Western diet feedingEpithelium-derived factorWnt/β-cateninHuman HCC cellsHuman HCC specimensInhibits Wnt/β-cateninMultiple tumor typesPEDF knockoutCarcinoma cell linesDiet feedingKO miceWestern dietHepatocellular carcinoma cell linesHCC formationHuman hepatocellular carcinoma cell lineTumor-suppressive propertiesPigment epitheliumTumor typesWnt5a proteinControl livers
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 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