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 deletion
2019
Activation of DNA Damage Response and Cellular Senescence in Cardiac Fibroblasts Limit Cardiac Fibrosis After Myocardial Infarction
Shibamoto M, Higo T, Naito AT, Nakagawa A, Sumida T, Okada K, Sakai T, Kuramoto Y, Yamaguchi T, Ito M, Masumura Y, Higo S, Lee JK, Hikoso S, Komuro I, Sakata Y. Activation of DNA Damage Response and Cellular Senescence in Cardiac Fibroblasts Limit Cardiac Fibrosis After Myocardial Infarction. International Heart Journal 2019, 60: 944-957. PMID: 31257341, DOI: 10.1536/ihj.18-701.Peer-Reviewed Original ResearchConceptsCellular senescenceDNA damage response systemDNA damage responseCardiac fibroblastsDDR activationDamage responseMolecular mechanismsSenescenceGene deletionJuxtacrine mannerProliferation of CFsCardiac fibrosisCF proliferationProliferationCardiac remodelingActivationTissue fibrosisRemodelingImportant roleTherapeutic strategiesRoleRecent reportsDeletionRegulationATM gene deletion
2018
Cardiomyocyte gene programs encoding morphological and functional signatures in cardiac hypertrophy and failure
Nomura S, Satoh M, Fujita T, Higo T, Sumida T, Ko T, Yamaguchi T, Tobita T, Naito AT, Ito M, Fujita K, Harada M, Toko H, Kobayashi Y, Ito K, Takimoto E, Akazawa H, Morita H, Aburatani H, Komuro I. Cardiomyocyte gene programs encoding morphological and functional signatures in cardiac hypertrophy and failure. Nature Communications 2018, 9: 4435. PMID: 30375404, PMCID: PMC6207673, DOI: 10.1038/s41467-018-06639-7.Peer-Reviewed Original ResearchConceptsCardiac hypertrophyCardiomyocyte remodelingGene programHeart failurePressure overloadMorphological hypertrophyHeart functionHypertrophyP53 deletionEarly hypertrophyFunctional signaturesFunctional phenotypeLate hypertrophyP53 signalingTranscriptional signatureProgram activationMitochondrial inhibitionUnderlying mechanismCardiomyocyte identityCardiomyocytesMitochondrial activationRemodelingFailureTranscriptional programsActivation
2017
DNA single-strand break-induced DNA damage response causes heart failure
Higo T, Naito AT, Sumida T, Shibamoto M, Okada K, Nomura S, Nakagawa A, Yamaguchi T, Sakai T, Hashimoto A, Kuramoto Y, Ito M, Hikoso S, Akazawa H, Lee JK, Shiojima I, McKinnon PJ, Sakata Y, Komuro I. DNA single-strand break-induced DNA damage response causes heart failure. Nature Communications 2017, 8: 15104. PMID: 28436431, PMCID: PMC5413978, DOI: 10.1038/ncomms15104.Peer-Reviewed Original ResearchConceptsPressure overload-induced heart failureOverload-induced heart failureHeart failureSingle-strand breaksNF-κB signalingNew therapeutic strategiesSSB accumulationDDR activationInflammatory cytokinesTherapeutic strategiesUnrepaired single-strand breaksDNA damageDNA single-strand breaksCausative roleDNA damage responseGenetic deletionPathogenesisActivationPivotal roleFailureDamage responseHeartCritical roleCytokinesMice