Molecular Mechanisms of Muscular Regeneration
Grant-in-Aid for Scientific Research (B)
|Allocation Type||Single-year Grants |
Neurophysiology and muscle physiology
|Research Institution||Osaka University |
YAMAMOTO Hiroshi Osaka University, Graduate School of Pharmaceutical Sciences, Department of Immunology, Professor, 薬学研究科, 教授 (50127312)
TSUJIKAWA Kazutake Osaka University, Graduate School of Pharmaceutical Sciences, Department of Immunology, Associate Professor, 薬学研究科, 助教授 (10207376)
FUKADA Soichiro Osaka University, Graduate School of Pharmaceutical Sciences, Department of Immunology, Research Associate, 薬学研究科, 助手 (20432445)
|Project Period (FY)
2004 – 2006
Completed (Fiscal Year 2006)
|Budget Amount *help
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2006: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥7,800,000 (Direct Cost: ¥7,800,000)
|Keywords||Satellite Cell / Muscle Regeneration / Macrophage / Stem Cell / Cytokine / Gene Chip / Expressed Gene Profiling|
When muscle tissue is damaged by physical, chemical or biological stress, muscle fibers will be newly regenerated. The regeneration process of muscles is very complicated but well organized. The most important cell population for the muscle regeneration is a muscle satellite cell, which is a muscle specific tissue stem cell. Upon muscle damages, many inflammatory cells infiltrate into the damaged sites. Macrophage infiltration coincides with stem cell proliferation and muscle tube formation. This phenomenon suggested that macrophages act not only as a scavenger cells for clean up damaged muscle fibers but also as secretor cells for some cytokines which stimulates satellite cell proliferation and differentiation. When muscle regeneration was induced in the mice having lower numbers of macrophages, muscle regeneration efficiency was decreased. To clarify the roles of satellite cells and macrophages, we investigated the methods to purify them, and analyzed expressing gene profiles of these cell populations.
1.We established a novel monoclonal antibody, SM/C-2.6 which enabled us to isolate muscle satellite cells.
2.Applying the monoclonal antibody, purified SM/C-2.6-positive cells have muscle stem cell nature.
3.Expressing gene profile of satellite cell was analyzed.
4.In the absence of macrophages, we found that generation of fibrosis as well as severely impaired muscle regeneration.
5.Macrophages were purified from regenerating muscles and their expressing gene profile was analyzed.
6.As a factor for fibrosis-inducing molecule, a certain molecule belonging to a TGF-β family was identified.
7.A novel cell population which act as a fibrosis-inducing cell as identified.
8.Laminin is a important extracellular matrix molecule. We also found that the cell is a main cells source for laminin-producing cells.
These observations will contribute for understanding of molecular and cellular mechanisms of muscle regeneration, and will contribute for the therapy of muscular dystrophy.
Report (4 results)
Research Products (16 results)