Project/Area Number |
18K06706
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 47040:Pharmacology-related
|
Research Institution | Hoshi University |
Principal Investigator |
|
Co-Investigator(Kenkyū-buntansha) |
山田 岳史 日本医科大学, 医学部, 准教授 (50307948)
|
Project Period (FY) |
2018-04-01 – 2021-03-31
|
Project Status |
Completed (Fiscal Year 2020)
|
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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
Keywords | シスプラチン / 副作用 / 筋萎縮 / miRNA / 骨格筋萎縮 / バイオマーカー |
Outline of Final Research Achievements |
Comprehensive analysis revealed that mir-5129-5p was upregulated in both skeletal muscle and plasma in cisplatin-induced muscle atrophy of mice. However, this miRNA was not expressed in humans. Therefore, due to the species difference, applied research using serum samples of patients was not possible. On the other hand, it was clarified that the expression of the mir-29-3p family targeting IGF-1 and the expression of IGF-1 decreased in skeletal muscle in mouse of cisplatin-induced muscle atrophy, and the protein synthesis pathway was suppressed. Furthermore, it was suggested that cisplatin-induced muscle atrophy is suppressed by supplementing with IGF-1. This study suggested that the increased expression of the mir-29-3p family in skeletal muscle could be a diagnostic marker for cisplatin-induced muscle atrophy.
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Academic Significance and Societal Importance of the Research Achievements |
がん患者において進行性の骨格筋萎縮は予後予測因子となる。がん闘病中患者のこの骨格筋萎縮に対し、「簡便な診断マーカーにて、筋萎縮をより早く診断できるか」、「どう筋量を維持するか」が、臨床上の重要な課題である。そこで本申請では、シスプラチンの筋萎縮発症におけるバイオ(診断)マーカーを新たな視点である miRNA にて探索し、さらには筋萎縮の発症機序の解明を試みた結果、骨格筋中のmir-29-3pファミリーの発現増加はシスプラチンによる筋萎縮時の診断マーカーになり得ることが示唆できた。
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