2024
Intestinal Nogo-B reduces GLP1 levels by binding to proglucagon on the endoplasmic reticulum to inhibit PCSK1 cleavage
Gong K, Xue C, Feng Z, Pan R, Wang M, Chen S, Chen Y, Guan Y, Dai L, Zhang S, Jiang L, Li L, Wang B, Yin Z, Ma L, Iwakiri Y, Tang J, Liao C, Chen H, Duan Y. Intestinal Nogo-B reduces GLP1 levels by binding to proglucagon on the endoplasmic reticulum to inhibit PCSK1 cleavage. Nature Communications 2024, 15: 6845. PMID: 39122737, PMCID: PMC11315690, DOI: 10.1038/s41467-024-51352-3.Peer-Reviewed Original ResearchConceptsEnteroendocrine cellsEndoplasmic reticulum (ER)-resident proteinGlucagon-like peptide 1Nogo-BEndoplasmic reticulumStimulate insulin secretionPotential therapeutic targetProglucagonGlucagon-like peptide 1 receptorInhibit glucagon secretionRegulatory processesIntestinal tractProglucagon fragmentInsulin secretionCleavageNogo-B knockoutTherapeutic targetPancreatic cellsPeptide 1Glucagon secretionCellsReticulonGolgiReticulon 4BInsulin resistance
2022
Inhibition of high-fat diet–induced obesity via reduction of ER-resident protein Nogo occurs through multiple mechanisms
Wang X, Yang Y, Zhao D, Zhang S, Chen Y, Chen Y, Feng K, Li X, Han J, Iwakiri Y, Duan Y, Yang X. Inhibition of high-fat diet–induced obesity via reduction of ER-resident protein Nogo occurs through multiple mechanisms. Journal Of Biological Chemistry 2022, 298: 101561. PMID: 34998825, PMCID: PMC8814669, DOI: 10.1016/j.jbc.2022.101561.Peer-Reviewed Original ResearchConceptsHigh-fat dietMetabolic disordersHigh-fat diet-induced obesityBody mass index valuesInhibition of NogoSerum proinflammatory cytokinesDiet-induced obesityInfiltration of macrophagesType 2 diabetesWT littermate control miceLittermate control miceEffects of NogoMass index valuesBrown adipose tissueProtect miceNormal chowControl miceProinflammatory cytokinesInsulin resistanceObesity treatmentRisk factorsLipid profileCardiovascular diseaseProtein NogoObesity
2020
Reduced Nogo expression inhibits diet-induced metabolic disorders by regulating ChREBP and insulin activity
Zhang S, Guo F, Yu M, Yang X, Yao Z, Li Q, Wei Z, Feng K, Zeng P, Zhao D, Li X, Zhu Y, Miao QR, Iwakiri Y, Chen Y, Han J, Duan Y. Reduced Nogo expression inhibits diet-induced metabolic disorders by regulating ChREBP and insulin activity. Journal Of Hepatology 2020, 73: 1482-1495. PMID: 32738448, DOI: 10.1016/j.jhep.2020.07.034.Peer-Reviewed Original ResearchConceptsDiet-induced metabolic disordersHepatic lipid accumulationInsulin sensitivityMetabolic disordersInsulin resistanceNogo expressionNon-alcoholic fatty liver diseaseDiet-induced body weight gainInsulin activityDiet-induced glucose intoleranceLipid accumulationFatty liver diseaseHigh-fructose dietGrowth factor 21Littermate control miceDe novo lipogenesisHigh-carbohydrate dietBody weight gainCarbohydrate-responsive element-binding proteinExpression of ChREBPChREBP activityEndoplasmic reticulum stressMetabolic complicationsGlucose intoleranceLiver disease
2019
Poly(amine-co-ester) nanoparticles for effective Nogo-B knockdown in the liver
Cui J, Piotrowski-Daspit AS, Zhang J, Shao M, Bracaglia LG, Utsumi T, Seo YE, DiRito J, Song E, Wu C, Inada A, Tietjen GT, Pober JS, Iwakiri Y, Saltzman WM. Poly(amine-co-ester) nanoparticles for effective Nogo-B knockdown in the liver. Journal Of Controlled Release 2019, 304: 259-267. PMID: 31054286, PMCID: PMC6613984, DOI: 10.1016/j.jconrel.2019.04.044.Peer-Reviewed Original Research
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
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