2004 Fiscal Year Final Research Report Summary
Moduration of myostatin activity through extracellular matrix
| Project/Area Number |
14360156
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Zootechnical science/Grassland science
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| Research Institution | Hokkaido University |
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Principal Investigator |
NISHIMURA Takanori Hokkaido University, Graduate School of Agriculture, Associate Professor, 大学院・農学研究科, 助教授 (10237729)
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| Co-Investigator(Kenkyū-buntansha) |
HATTORI Akihito Hokkaido University, Graduate School of Agriculture, Professor, 大学院・農学研究科, 教授 (50125027)
MORI Tadashi Hokkaido University, Graduate School of Agriculture, Assistant Professor, 大学院・農学研究科, 助手 (30230072)
WAKAMATSU Jun-ichi Hokkaido University, Graduate School of Agriculture, Assistant Professor, 大学院・農学研究科, 助手 (30344493)
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| Project Period (FY) |
2002 – 2004
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| Keywords | myostatin / decorin / muscle cell / proliferation / extracellular matrix / skeletal muscle |
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| Research Abstract |
Myostatin, a member of TGF-β superfamily of growth factors, acts as a negative regulator of skeletal muscle mass. The mechanism whereby myostatin controls the proliferation and differentiation of myogenic cells is mostly clarified. However, the regulation of myostatin activity to myogenic cells after its secretion in the extracellular matrix (ECM) is still unknown. Decorin, a small leucine-rich proteoglycan, binds TGF-β and regulates its activity in the ECM. Thus, we hypothesized that decorin could also bind to myostatin and participate in modulation of its activity to myogenic cells. In order to test the hypothesis, we investigated the interaction between myostatin and decorin by surface plasmon assay. Decorin interacted with mature myostatin in the presence of concentrations of Zn^<2+> greater than 10 μM, but not in the absence of Zn^<2+>. Kinetic analysis with a 1:1 binding model resulted in dissociation constants (K_D) of 2.02×10^<-8> M and 9.36×10^<-9> M for decorin and the core protein of decorin, respectively. Removal of the glycosaminoglycan chain by chondroitinase ABC digestion did not affect binding, suggesting that decorin could bind to myostatin with its core protein. Furthermore, we demonstrated that immobilized decorin could rescue the inhibitory effect of myostatin on myoblast proliferation in vitro. These results suggest that decorin could trap myostatin and modulate its activity to myogenic cells in the ECM.
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