| Project/Area Number |
16K15410
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
General internal medicine(including psychosomatic medicine)
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| Research Institution | Nagoya University |
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Principal Investigator |
GOTO HIROKI 名古屋大学, 医学部附属病院, 医員 (50770913)
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| Research Collaborator |
INOUE Aiko 名古屋大学, 未来社会創造機構, 特任助教
KIMURA Kaoru 名古屋大学, 大学院医学系研究科, 客員研究者
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 骨格筋再生 / サルコペニア / 骨格筋障害 / 骨格筋分化 / 老年医学 |
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| Outline of Final Research Achievements |
We have reported that apoptotic cells-derived growth factor (called GFX) regulated vascular smooth muscle cell proliferation and neointimal formation in response to injury. Cardiotoxin(CTX) was injected into the left gastrocnemius muscle of mice. We observed injured muscle had increased GFX gene and protein expressions. GFX blocking with its neutralizing antibody accelerated CTX related muscle changes in microstructure and performance. The amounts of proteins or mRNAs for p-Akt, p-mTOR and p-p38MAPK, Pax7, and MyoD and the numbers of CD34+/integrin-α7+ MuSCs and proliferating cells in the muscles and bone-marrow were reduced by GFX depletion; and these changes were improved by the treatment with mouse recombinant GFX(r-GFX). Finally, we observed that r-GFX also ameliorated muscle changes in microstructure and performance. These findings suggest that apoptosis-driven expression of GFX is thus a novel target for the treatment of apoptosis-based muscle disorder.
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| Academic Significance and Societal Importance of the Research Achievements |
骨格筋では加齢、廃用、脱神経など様々な要因で障害が起こるとされ、障害後の骨格筋細胞のアポトーシスや筋衛星細胞の再生不全は、サルコペニアの発症・進展の要因の一つであると知られている。申請者グループが血管障害実験において見出したGFX(growth factor-X)が、骨格筋障害後の筋再生およびリモデリングへ関与していることを提唱し、本研究に置いてGFXが障害筋肉組織における骨格筋細胞再生に明らかに関与していることを証明した。本研究成果により、GFXが今後、サルコペニアや骨格筋再生治療の分子標的として臨床応用につなげ得ることが期待される。
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