| Project/Area Number |
16K19636
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Pediatrics
|
|---|
| Research Institution | Shinshu University |
|---|
Principal Investigator |
Shiba Naoko 信州大学, 再生医科学教室, 助教(特定雇用) (00639289)
|
|---|
| Research Collaborator |
NAKAMURA Akinori 信州大学, 医学部, 特任教授 (10303471)
MIYAZAKI Daigo 信州大学, 医学部附属病院, 講師 (80596370)
|
|---|
| Project Period (FY) |
2016-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
|
|---|
| Keywords | 筋ジストロフィー / MMP-9 / オステオポンチン |
|---|
| Outline of Final Research Achievements |
At a month of age, the dystrophic muscles of mdx/Mmp9-/- mice showed reduced necrosis and neutrophil invasion, accompanied by down-regulation of MIP-2. In addition, muscle regeneration was enhanced, which coincided with increased M2 macrophage infiltration and upregulation of MCP-1 and resulted in increased muscle strength. It also displayed an accelerated upregulation of osteopontin and hyaluronan expression colocalized with CD44, a receptor of MMP9 at the stage. However, in the later stage at one year of age, the mice exhibited muscle growth impairment through altered expression of myogenic factors and increased fibroadipose tissue. These results showed that MMP-9 might have multiple functions during disease progression. A therapy targeting MMP-9 may improve muscle pathology and function at the early disease stage, but the continuous inhibition of this protein may result in the accumulation of fibroadipose tissues and reduced muscle strength at the late disease stage.
|
| Academic Significance and Societal Importance of the Research Achievements |
mdxマウスの骨格筋変性における MMP-9 およびヒアルロン酸、OPNの役割、相互作用を解明することは、ジストロフィン欠損が引き起こす様々な分子機構の一端を解明するのみでなく、治療効果評価のための病勢マーカーの確立やステロイド剤に代わる新たな治療法の開発につながる可能性がある。
|
