Analysis of TGF-beta family regulating muscle atrophy, fibrosis and fatty degeneration
| Project/Area Number |
16K08599
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
General medical chemistry
|
|---|
| Research Institution | Fujita Health University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
常陸 圭介 藤田医科大学, 総合医科学研究所, 助教 (10508469)
中谷 直史 藤田医科大学, 総合医科学研究所, 助教 (00421264)
|
|---|
| Project Period (FY) |
2016-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| Keywords | 筋萎縮 / 筋分化制御 / 異所性脂肪 / TGF-βファミリー / マイオジェニン / 長鎖非翻訳RNA / 間葉系幹細胞 / ドラッグリポジショニング / 非翻訳RNA / BMP / 筋肥大 / 薬剤スクリーニング / 加齢性筋萎縮 / 悪液質 / 非翻訳核酸 / 脂肪化 / 異所性骨化 / 薬剤探索 / TGF-β / 筋分化 / 質量分析 / サルコペニア筋萎縮 / 筋分化制御因子 / 次世代型網羅的解析 / TGF-β ファミリー |
|---|
| Outline of Final Research Achievements |
We have identified a novel antisense lncRNA derived from myogenin promoter. It is expressed with myogenin during muscle differentiation and is found essential for myogenesis. Using RNA pulldown and comprehensive proteomic analyses, DEAD-box protein, Ddx17, was identified as one of the lncRNA interacting proteins. By in vivo electroporation, knockdown of the lncRNA was effective to ameliorate neurogenic muscle atrophy. BMP/GDF family member was found upregulated during recovery from muscle atrophy by lncRNA knockdown. By using sophisticated differentiation culture system of mesenchymal stem cells from human skeletal muscle and drug screening, anti-histamine drugs were identified as inhibitors of ectopic fat generation and ectopic bone formation in skeletal muscle both in vitro and in vivo.
|
| Academic Significance and Societal Importance of the Research Achievements |
骨格筋は、生体最重量組織であるが、病態では、筋萎縮、異性脂肪化、骨化が見られ、生活の質の低下につながる。超高齢化社会を迎えた本邦では、サルコペニアが重要な疾患概念として認知されている。マイオジェニンは、胎生期の骨格筋で発現され筋形成を担うが、神経損傷時にも発現誘導される重要な転写因子である。本研究の成果から、新規長鎖非翻訳RNAによるマイオジェニンの新たな制御機構が明らかとなり、筋萎縮緩和に応用可能であることが解析され、社会的な意義は大きい。独自に開発した培養系による既存薬のスクリーニングで、異性脂肪化と骨化抑制役候補を見出し、生体でも効果があることを示したことは波及効果が大きい。
|
Report
(4 results)
Research Products
(46 results)
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Journal Article] UBL3 modification influences protein sorting to small extracellular vesicles.2018
Author(s)
Ageta H, Ageta-Ishihara N, Hitachi K, Karayel O, Onouchi T, Yamaguchi H, Kahyo T, Hatanaka K, Ikegami K, Yoshioka Y, Nakamura K, Kosaka N, Nakatani M, Uezumi A, Ide T, Tsutsumi Y, Sugimura H, Kinoshita M, Ochiya T, Mann M, Setou M, Tsuchida K.
-
Journal Title
Nature Communications
Volume: 9
Issue: 1
Pages: 3936-3936
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
-
-
-
[Journal Article] Cell-surface protein profiling identifies distinctive markers of progenitor cells in human skeletal muscle.2016
Author(s)
Uezumi A, Nakatani M, Ikemoto-Uezumi M, Yamamoto N, Morita M, Yamaguchi A, Yamada H, Kasai T, Masuda S, Narita A, Miyagoe-Suzuki Y, Takeda S, Fukada S, Nishino I, Tsuchida K.
-
Journal Title
Stem Cell Reports.
Volume: 7
Issue: 2
Pages: 263-278
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
