2022 Fiscal Year Final Research Report
Elucidation of principle of novel non-coding nucleic acids acting on skeletal muscle differentiation and muscle atrophy and application to treatment for muscle atrophy
| Project/Area Number |
19H03427
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 48040:Medical biochemistry-related
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| Research Institution | Fujita Health University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
中谷 直史 星城大学, リハビリテーション学部, 准教授 (00421264)
常陸 圭介 藤田医科大学, 医科学研究センター, 講師 (10508469)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Keywords | 筋萎縮 / 筋肥大 / マイオカイン / サルコペニア / 非翻訳核酸 / アクトミオシン / 翻訳後修飾 / 悪液質 |
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| Outline of Final Research Achievements |
In this study, our group performed researches related to muscle atrophy. Myogenin is involved in myogenesis as well as muscle atrophy in adults. We characterized a functional role of a novel lncRNA called Myoparr. We also analyzed up-or down-regulated molecules in various muscle atrophy models. Mesenchymal progenitors located in muscle in involved in fatty degeneration and fibrosis. Intriguingly, we have found that the depletion of mesenchymal progenitors, also known as FAP cells, serves as a muscle atrophy model. Gdf10, one of the TGF-beta superfamily members, was found downregulated in sarcopenia and atrophy models. Continuous Gdf10 supply recovered muscle atrophy and other sarcopenia-related neuromuscular changes. Double Myh1 and 4 mutated mice were established. They turned out to serve as a novel muscle atrophy model with disruption of sarcomere structure. Both atrophic signal and protein degradation signals were upregulated.
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| Free Research Field |
分子細胞生物学
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| Academic Significance and Societal Importance of the Research Achievements |
人生100年の超高齢社会を迎え筋萎縮が社会的な問題となっている。その病態解明と対応は重要な課題である。筋萎縮病態の解明は、遺伝性筋疾患および筋萎縮をきたす種々の病態のために学術的及び社会的に意義がある。本研究で、筋萎縮を分子レベルで詳細に解析し、筋萎縮抑制標的を見出し解析を進捗させた。速筋型ミオシン重鎖の二重変異体を作製し、新たな高度筋萎縮モデルを確立した。骨格筋の幹細胞の一種である間葉系前駆細胞の除去が筋萎縮モデルとなり、Gdf10の減少が一因となることを示した。その補充で筋萎縮や周辺の神経筋接合部の異常が改善されることを示した。ミオシンの翻訳後修飾の生理的な意義についても解析を推進させた。
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