| Project/Area Number |
18K07423
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 52010:General internal medicine-related
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| Research Institution | Keio University |
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Principal Investigator |
Endo Jin 慶應義塾大学, 医学部(信濃町), 講師 (50398608)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | サルコペニア / 老化 / Wnt-βカテニンシグナル / プロレニン受容体 / YAPシグナル / 細胞融合 / 早熟分化 / Wntシグナル / オートファジー / Ｗｎｔシグナル |
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| Outline of Final Research Achievements |
Prevention of age-related skeletal muscle atrophy, so called sarcopenia, is important for extending healthy life expectancy. We revealed that the prorenin receptor PRR, which was conventionally known as a blood pressure regulator, was involved in the pathogenesis of sarcopenia by activating Wnt-β-catenin signaling , which are closely related to aging, and YAP signaling. Activation of the PRR-Wnt signaling axis induced premature differentiation of muscle cells to inhibit myoblast fusion, resulting in the atrophy of muscle fibers, especially fast fibers. PRR-neutralizing antibodies, Wnt inhibitors, and YAP inhibitors each exhibited the effect of restoring muscle atrophy, and showed the potential to be a therapeutic drug for sarcopenia.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、高齢化を迎える日本において、元気に健康を維持したまま生活できる期間、いわゆる健康寿命は、平均寿命にくらべ10年前後も短く、この予防および治療は現代医療の喫緊の課題といえます。健康寿命の低下に寄与する最も大きな因子の一つが、加齢性骨格筋萎縮によるADLの低下です。我々の研究で得られた成果から、加齢性骨格筋萎縮に関係する分子とシグナル経路（PRR-Wnt-YAPシグナル）を抑える薬剤が治療薬の可能性を持っていることが明らかになりました。従来、加齢による筋肉の減少は不可避な老化現象とみなされてきましたが、本研究の結果からも治療介入可能な病態・疾患の一つと考えられます。
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