ID | 58080 |
フルテキストURL | |
著者 |
Ujihara, Yoshihiro
Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Kanagawa, Motoi
Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine
Mohri, Satoshi
Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Takatsu, Satomi
Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Kobayashi, Kazuhiro
Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine
Toda, Tatsushi
Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine
Naruse, Keiji
Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
ORCID
Kaken ID
publons
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Katanosaka, Yuki
Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
ORCID
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抄録 | Heart failure is the major cause of death for muscular dystrophy patients, however, the molecular pathomechanism remains unknown. Here, we show the detailed molecular pathogenesis of muscular dystrophy-associated cardiomyopathy in mice lacking the fukutin gene (Fktn), the causative gene for Fukuyama muscular dystrophy. Although cardiac Fktn elimination markedly reduced alpha-dystroglycan glycosylation and dystrophin-glycoprotein complex proteins in sarcolemma at all developmental stages, cardiac dysfunction was observed only in later adulthood, suggesting that membrane fragility is not the sole etiology of cardiac dysfunction. During young adulthood, Fktn-deficient mice were vulnerable to pathological hypertrophic stress with downregulation of Akt and the MEF2-histone deacetylase axis. Acute Fktn elimination caused severe cardiac dysfunction and accelerated mortality with myocyte contractile dysfunction and disordered Golgi-microtubule networks, which were ameliorated with colchicine treatment. These data reveal fukutin is crucial for maintaining myocyte physiology to prevent heart failure, and thus, the results may lead to strategies for therapeutic intervention.
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発行日 | 2019-12-17
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出版物タイトル |
Nature Communications
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巻 | 10巻
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出版者 | Nature Publishing Group
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開始ページ | 5754
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ISSN | 2041-1723
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資料タイプ |
学術雑誌論文
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言語 |
英語
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OAI-PMH Set |
岡山大学
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著作権者 | © The Author(s) 2019
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論文のバージョン | publisher
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PubMed ID | |
DOI | |
Web of Science KeyUT | |
関連URL | isVersionOf https://doi.org/10.1038/s41467-019-13623-2
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ライセンス | http://creativecommons.org/licenses/by/4.0/
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助成機関名 |
文部科学省
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助成番号 | 17H02085
18K19924
17H04740
10104401
17H06421
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