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Moduration of myostatin activity through extracellular matrix

Research Project

Project/Area Number 14360156
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Zootechnical science/Grassland science
Research InstitutionHokkaido University

Principal Investigator

NISHIMURA Takanori  Hokkaido University, Graduate School of Agriculture, Associate Professor, 大学院・農学研究科, 助教授 (10237729)

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)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥10,500,000 (Direct Cost: ¥10,500,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2002: ¥7,700,000 (Direct Cost: ¥7,700,000)
Keywordsmyostatin / decorin / muscle cell / proliferation / extracellular matrix / skeletal muscle / 増殖・分化
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.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (4 results)

All 2006 2005

All Journal Article (4 results)

  • [Journal Article] Decorin binds myostatin and modulates its activity to muscle cells2006

    • Author(s)
      Miura, et al.
    • Journal Title

      Biochemical and Biophysical Research Communications 340(2)

      Pages: 675-680

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Decorin binds myostatin and modulates its activity to muscle cells2006

    • Author(s)
      Miura et al.
    • Journal Title

      Biochemical and Biophysical Research Communications 340(2)

      Pages: 675-680

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Improved muscle healing through enhanced regeneration and reduced fibrosis in myostatin-null mice2005

    • Author(s)
      McCroskery, et al.
    • Journal Title

      Journal of Cell Science 118

      Pages: 3531-3541

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Improved muscle healing through enhanced regeneration and reduced fibrosis in myostatin-null mice2005

    • Author(s)
      McCroskery et al.
    • Journal Title

      Journal of Cell Science 118

      Pages: 3531-3541

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary

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Published: 2002-04-01   Modified: 2016-04-21  

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