Featured Publications
Complement C1q-induced activation of β-catenin signalling causes hypertensive arterial remodelling
Sumida T, Naito AT, Nomura S, Nakagawa A, Higo T, Hashimoto A, Okada K, Sakai T, Ito M, Yamaguchi T, Oka T, Akazawa H, Lee JK, Minamino T, Offermanns S, Noda T, Botto M, Kobayashi Y, Morita H, Manabe I, Nagai T, Shiojima I, Komuro I. Complement C1q-induced activation of β-catenin signalling causes hypertensive arterial remodelling. Nature Communications 2015, 6: 6241. PMID: 25716000, PMCID: PMC4351572, DOI: 10.1038/ncomms7241.Peer-Reviewed Original ResearchConceptsVascular smooth muscle cellsProliferation of VSMCsArterial remodellingΒ-catenin signalingΒ-cateninComplement C1qBlood pressure elevationEnd-organ damageNovel therapeutic targetSmooth muscle cellsMacrophage depletionImmune cellsPrecise molecular mechanismsTherapeutic targetStructural remodellingMuscle cellsRemodellingHypertensionArteriosclerosisComplement C1ActivationC1qMolecular mechanismsSignalingGene deletionActivated β-catenin in Foxp3+ regulatory T cells links inflammatory environments to autoimmunity
Sumida T, Lincoln MR, Ukeje CM, Rodriguez DM, Akazawa H, Noda T, Naito AT, Komuro I, Dominguez-Villar M, Hafler DA. Activated β-catenin in Foxp3+ regulatory T cells links inflammatory environments to autoimmunity. Nature Immunology 2018, 19: 1391-1402. PMID: 30374130, PMCID: PMC6240373, DOI: 10.1038/s41590-018-0236-6.Peer-Reviewed Original ResearchConceptsProstaglandin E receptor 2Regulatory T cellsTreg cellsT cellsAnti-inflammatory cytokine productionIL-10 productionPeripheral immune toleranceIL-10 expressionΒ-cateninE receptor 2Treg subpopulationsTreg phenotypeIL-10Cytokines IFNImmune toleranceTreg signatureCytokine signatureMultiple sclerosisAutoimmune diseasesCytokine productionInflammatory environmentLethal autoimmunityReceptor 2Activated β-cateninIFN
2016
Activation of endothelial β-catenin signaling induces heart failure
Nakagawa A, Naito AT, Sumida T, Nomura S, Shibamoto M, Higo T, Okada K, Sakai T, Hashimoto A, Kuramoto Y, Oka T, Lee JK, Harada M, Ueda K, Shiojima I, Limbourg FP, Adams RH, Noda T, Sakata Y, Akazawa H, Komuro I. Activation of endothelial β-catenin signaling induces heart failure. Scientific Reports 2016, 6: 25009. PMID: 27146149, PMCID: PMC4857119, DOI: 10.1038/srep25009.Peer-Reviewed Original ResearchConceptsWnt/β-cateninHeart failureCardiac dysfunctionCa miceEndothelial cellsΒ-cateninEndothelial β-cateninProgressive cardiac dysfunctionCardiac endothelial cellsDegeneration of mitochondriaArterial endothelial cellsNeuregulin-ErbB signalingNeuregulin proteinΒ-catenin-dependent canonical WntEndothelial expressionIschemic diseasesTherapeutic targetDysfunctionMiceSustained activationFunction mutationsNeuregulin-ErbBT-tubulesCanonical WntConditional gain
2015
Wnt/&bgr;-Catenin Signaling Contributes to Skeletal Myopathy in Heart Failure via Direct Interaction With Forkhead Box O
Okada K, Naito AT, Higo T, Nakagawa A, Shibamoto M, Sakai T, Hashimoto A, Kuramoto Y, Sumida T, Nomura S, Ito M, Yamaguchi T, Oka T, Akazawa H, Lee JK, Morimoto S, Sakata Y, Shiojima I, Komuro I. Wnt/&bgr;-Catenin Signaling Contributes to Skeletal Myopathy in Heart Failure via Direct Interaction With Forkhead Box O. Circulation Heart Failure 2015, 8: 799-808. PMID: 26038536, DOI: 10.1161/circheartfailure.114.001958.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBeta CateninCardiomyopathy, DilatedCell LineComplement C1qDisease Models, AnimalForkhead Box Protein O1Forkhead Transcription FactorsMice, TransgenicMuscle FatigueMuscle Fibers, SkeletalMuscle, SkeletalMuscular DiseasesRNA InterferenceTransfectionWnt Signaling PathwayWnt3A ProteinConceptsChronic heart failureFiber type shiftFatigable fibersSkeletal myopathyActivation of WntHeart failureModel miceCardiomyopathy miceSkeletal muscleNovel therapeutic targetMediator β-cateninType IIB fibersControl miceType shiftC2C12 cellsTherapeutic targetSignaling contributesComplement C1qMyopathyMiceCritical roleIIB fibersForkhead box OΒ-cateninFoxO1 activity