| Project/Area Number |
18K10987
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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 59040:Nutrition science and health science-related
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| Research Institution | Gunma University |
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Principal Investigator |
Yamada Eijiro 群馬大学, 医学部附属病院, 講師 (60645563)
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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 |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | Fyn / オートファジー / サルコペニア / メタボリック症候群 / sarcopenia / autophagy / STAC3 |
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| Outline of Final Research Achievements |
We focused on autophagy as a system that can regulate both sarcopenia and metabolic syndrome in skeletal muscle and revealed that non-receptor tyrosine kinase Fyn not only participates in metabolic syndrome but also regulates autophagy regulating sarcopenia through STAT3 regulation, mainly using transgenic mice (Cell metabolism 2010, Cell Rep. 2012).
We proceeded with further studies and demonstrating that Fyn-dependent STAT3 phosphorylation by IL6 was observed in mouse C2C12 myotube cells. Autophagy was decreased in those cells by both IL6-dependent and Fyn-dependent mechanisms. Furthermore, in the denervated mouse model, both Fyn and IL6 gene expressions were increased while the autophagy activity was decreased. We next introduced a hind limb suspension mouse model. We found that increased IL6 and STAT3 expression/phosphorylation and decreased autophagy activity. These results strongly suggest that Fyn is involved in the pathogenesis of sarcopenia.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究結果はFynがメタボリックシンドロームだけでなくサルコペニアの病因にも関与していることを示唆している。近年、肥満があるにもかかわらず、サルコペニアである状態、サルコペニア肥満が問題となってきている。こうした病態ではエネルギー管理をどの様に持っていくかが困難である。さらにサルコペニアに関しては現時点で薬物治療は限定的である。一方でFynはチロシンキナーゼであり、チロシンキナーゼの阻害薬は現時点でも多くが上市されてきている。本研究成果によりサルコペニア肥満の病因のより良い理解と治療法の開発につながる可能性があります。
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