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Matrix metalloproteinases as a therapeutic target of sarcoglycan-deficient muscular dystrophy

Research Project

Project/Area Number 21591101
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionKawasaki Medical School

Principal Investigator

SUNADA Yoshihide  川崎医科大学, 医学部, 教授 (00240713)

Co-Investigator(Kenkyū-buntansha) OHSAWA Yutaka  川崎医科大学, 医学部, 講師 (80246511)
MURAKAMI Tatsufumi  川崎医科大学, 医学部, 准教授 (30330591)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords神経分子病態学1 / 筋ジストロフィー / 再生医療 / シグナル伝達 / 発生・分化 / 神経科学
Research Abstract

Processing of β-dystroglycan(β-DG) by matrix metalloproteinases(MMPs) has been considered to play a fundamental role in muscle degeneration in sarcoglycan(SG)-deficient muscular dystrophy. Here we generate triple knockout(TKO) mice deficient to MMP-2, MMP-9, and γ-SG to investigate in vivo processing of β-DG by MMP-2, MMP-9.Muscle pathology of TKO mice was comparable to that of γ-SG-knockout mice. Unexpectedly, the 30-kDa-processed form of β-DG was present in TKO mouse muscles likewise γ-SG-null mouse muscles. These findings indicate that MMPs other than MMP-2/9 participate in the molecular mechanism underlying the processing of β-DG in sarcoglycan-deficient muscular dystrophy.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (30 results)

All 2012 2011 2010 2009

All Journal Article (10 results) (of which Peer Reviewed: 10 results) Presentation (19 results) Book (1 results)

  • [Journal Article] An inhibitor of transforming growth factor beta type I receptor ameliorates muscle atrophy in a mouse model of caveolin 3-deficient muscular dystrophy2012

    • Author(s)
      Ohsawa Y, Okada T, Nishimatsu SI, Ishizaki M, Suga T, Fujino M, Murakami T, Uchino M, Tsuchida K, Noji S, Hinohara A, Shimizu T, Shimizu K, Sunada Y
    • Journal Title

      Lab Invest

      Volume: 78 Issue: 8 Pages: 1100-1114

    • DOI

      10.1038/labinvest.2012.78

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Endoplasmic reticulum stress response in P104L mutant caveolin-3 transgenic mice2011

    • Author(s)
      Kuga A, Ohsawa Y, Okada T, Kanda F, Kanagawa M, Toda T, Sunada Y.
    • Journal Title

      Hum Mol Genet

      Volume: 20(15) Issue: 15 Pages: 2975-2983

    • DOI

      10.1093/hmg/ddr201

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Atelocollagen-mediated systemic administration ofmyostatin-targeting siRNA improves muscular atrophy in caveolin-3-deficient mice2011

    • Author(s)
      Kawakami E, Kinouchi N, Adachi T, Ohsawa Y, Ishimaru N, Ohuchi H, Sunada Y, Hayashi Y, Tanaka E, Noji S.
    • Journal Title

      Dev Growth Differ

      Volume: 53 Issue: 1 Pages: 48-54

    • DOI

      10.1111/j.1440-169x.2010.01221.x

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Follistatin-derived peptide expression in muscle decreases adipose tissue mass and prevents hepatic steatosis2011

    • Author(s)
      Nakatani M, Kokubo M, Ohsawa Y, Sunada Y, Tsuchida K.
    • Journal Title

      Am J Physiol Endocrinol Metab

      Volume: 300 Issue: 3 Pages: 543-553

    • DOI

      10.1152/ajpendo.00430.2010

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Follistatin-derived peptide expression in muscle decreases adiposetissue mass and prevents hepatic steatosis.2011

    • Author(s)
      Nakatani M, Kokubo M, Ohsawa Y, Sunada Y, Tsuchida K.
    • Journal Title

      Am J Physiol Endocrinol Metab

      Volume: 300(3)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Atelocollagen-mediated systemic administration of myostatin-targeting siRNA improves muscular atrophy in caveolin-3-deficient mice.2011

    • Author(s)
      Kawakami E, Kinouchi N, Adachi T, Ohsawa Y, Ishimaru N, Ohuchi H, Sunada Y, Hayashi Y, Tanaka E, Noji S.
    • Journal Title

      Dev Growth Differ

      Volume: 53(1) Pages: 48-54

    • NAID

      10027899274

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rapid screening for Japanese dysferlinopathy by fluorescent primer extension2010

    • Author(s)
      Hayashi S, Ohsawa Y, Takahashi T, Suzuki N, Okada T, Rikimaru M, Murakami T, Aoki M, Sunada Y.
    • Journal Title

      Intern Med

      Volume: 49 Pages: 2693-2696

    • NAID

      130000413429

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] The transthyretin gene is expressed in Schwann cells of peripheral nerves2010

    • Author(s)
      Murakami T, Ohsawa Y, Zhenghua L, Yamamura K, Sunada Y.
    • Journal Title

      Brain Res

      Volume: 1348 Pages: 222-225

    • DOI

      10.1016/j.brainres.2010.06.017

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hereditary sensory ataxic neuropathy associated with proximal muscle weakness in the lower extremities2010

    • Author(s)
      Murakami T, Fukai Y, Rikimaru M, Henmi S, Ohsawa Y, Sunada Y.
    • Journal Title

      J Neurol Sci

      Volume: 291 Issue: 1-2 Pages: 121-123

    • DOI

      10.1016/j.jns.2009.12.011

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Rapid Screening for Japanese Dysferlinopathy by Fluorescent Primer Extension.2010

    • Author(s)
      Hayashi S, Ohsawa Y, Takahashi T, Suzuki N, Okada T, Rikimaru M, Murakami T, Aoki M, Sunada Y.
    • Journal Title

      Int Med

      Volume: 49 Pages: 2693-2696

    • NAID

      130000413429

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] TGF-betaシグナルナル制御による筋疾患治療法の開発2011

    • Author(s)
      大澤裕、砂田芳秀、岡田只士、西松伸一郎、林良雄、土田邦博、野地澄晴
    • Organizer
      平成23年度厚生労働省精神・神経疾患研究委託費筋ジストロフィー「西野班」班会議
    • Place of Presentation
      東京
    • Year and Date
      2011-12-06
    • Related Report
      2011 Final Research Report
  • [Presentation] 筋ジストロフィーの新時代の治療2011

    • Author(s)
      砂田芳秀
    • Organizer
      第29回日本神経治療学会総会
    • Place of Presentation
      ホテルフジタ福井(招待講演)
    • Year and Date
      2011-11-17
    • Related Report
      2011 Annual Research Report
  • [Presentation] Sarcolemmal nNOS prevents muscular wasting in a caveolin-3-deficeint muscular dystrophy 1C model2011

    • Author(s)
      Ohsawa, Sunada Y, et al
    • Organizer
      International Congress of Muscle Wasting 2011
    • Place of Presentation
      Centro Stefano Franscini Monte Verita, Switzerland
    • Year and Date
      2011-09-21
    • Related Report
      2011 Annual Research Report
  • [Presentation] Wound-healing MRL-MpJ phenotype improves outcome of dystrophin deficient mdx mice2011

    • Author(s)
      Sunada Y, Ohsawa Y, Fujino M, Okada T, Hayashi S, Rikimaru M, Murakami T, Nishimatsu SI, Nohno T, Nagao M
    • Organizer
      XII. International Congress on Neuromuscular Diseases
    • Place of Presentation
      Naples, Italy
    • Year and Date
      2011-07-21
    • Related Report
      2011 Final Research Report
  • [Presentation] シンポジウム:筋疾患に対する抗マイオスタチン抗体療法の開発と応用2011

    • Author(s)
      砂田芳秀
    • Organizer
      2011年日本神経学会学術大会シンポジウム
    • Place of Presentation
      名古屋
    • Year and Date
      2011-05-20
    • Related Report
      2011 Final Research Report
  • [Presentation] シンポジウム32:神経疾患に対する抗体療法:筋疾患に対する抗マイオスタチン抗体療法の開発と応用2011

    • Author(s)
      砂田芳秀
    • Organizer
      第52回日本神経学会学術大会
    • Place of Presentation
      名古屋国際会議場(招待講演)
    • Year and Date
      2011-05-20
    • Related Report
      2011 Annual Research Report
  • [Presentation] Caveolin-3高発現マウス骨格筋の解析2011

    • Author(s)
      砂田芳秀
    • Organizer
      第52回日本神経学会学術大会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2011-05-20
    • Related Report
      2011 Annual Research Report
  • [Presentation] シンポジウム:骨格筋再生療法2011

    • Author(s)
      大澤裕
    • Organizer
      2011年日本神経学会学術大会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-05-19
    • Related Report
      2011 Final Research Report
  • [Presentation] Sarcolemmal nNOS prevents muscular wasting in a caveolin-3-deficient limb-girdle muscular dystrophy 1C model2011

    • Author(s)
      Ohsawa Y, Fujino M, Okada S, Nishimatsu SI, Rikimaru M, Hayashi S, Nohno T, Sunada Y.
    • Organizer
      International congress of muscle wasting
    • Place of Presentation
      Ascona, Switzerland
    • Related Report
      2011 Final Research Report
  • [Presentation] Reprogrammed fibroblasts as a feasible source of cell-based therapy for muscular duystrophy2010

    • Author(s)
      Ohsawa Y, Okada T, Fujii I, Nishimatsu SI, Fujino M, Hayashi S, Rikimaru M, Murakami T, Nohno T, Sunada Y.
    • Organizer
      15th International Congress of World Muscle Society
    • Place of Presentation
      Kumamoto, Japan
    • Year and Date
      2010-12-10
    • Related Report
      2011 Final Research Report
  • [Presentation] 筋ジストロフィーに対する抗myostatin治療薬の開発,厚生労働省精神・神経疾患研究開発費「筋ジストロフィーおよびその関連疾患の分子病態解明、診断法確立と薬物治療の開発に関する研究」2010

    • Author(s)
      砂田芳秀、大澤裕、岡田只士、西松伸一郎、石崎雅俊、菅智宏、内野誠、濃野勉、野地澄晴、土田邦博
    • Organizer
      平成22年度「砂田班」班会議
    • Place of Presentation
      東京
    • Year and Date
      2010-12-03
    • Related Report
      2011 Final Research Report
  • [Presentation] Wound-healing MRL-MpJ phenotype improves outcome of dystrophin deficient mdx mice.2010

    • Author(s)
      Yoshihide Sunada, et al.
    • Organizer
      XII International Congress on Neuromuscular Diseases
    • Place of Presentation
      Naples, Italy
    • Year and Date
      2010-07-21
    • Related Report
      2010 Annual Research Report
  • [Presentation] 筋ジストロフィーの分子病態2010

    • Author(s)
      砂田芳秀
    • Organizer
      第28回日本神経治療学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2010-07-16
    • Related Report
      2011 Final Research Report
  • [Presentation] nNOSはcaveolin-3欠損症の病態を抑制する2010

    • Author(s)
      砂田芳秀
    • Organizer
      第51回日本神経学会総会
    • Place of Presentation
      東京
    • Year and Date
      2010-05-21
    • Related Report
      2011 Final Research Report
  • [Presentation] 線維芽細胞のdirectによる筋ジストロフィーの細胞治療2010

    • Author(s)
      砂田芳秀、大澤裕、岡田只士、藤野雅広、力丸満惠、林紗織、村上龍文、藤井績
    • Organizer
      平成21年度厚生労働省精神・神経疾患研究委託費筋ジストロフィー総合班会議
    • Place of Presentation
      東京
    • Year and Date
      2010-01-09
    • Related Report
      2011 Final Research Report
  • [Presentation] Reprogrammed fibroblasts are a source of cell therapy for caveolin-3-deficient and laminin α-2-deficient muscular dystrophies2010

    • Author(s)
      Ohsawa Y, Fujii I, Okada T, Nishimatsu SI, Hayashi S, Rikimaru M, Murakami T, Nohno T, Sunada Y.
    • Organizer
      2010 FASEB Summer Research Conferences : Skeletal Muscle Satellite and Stem Cells
    • Place of Presentation
      Arizona, USA
    • Related Report
      2011 Final Research Report
  • [Presentation] 線維芽細胞のdirect reprogrammingによる筋ジストロフィーの細胞治療2009

    • Author(s)
      砂田芳秀、大澤裕、岡田只士、藤野雅広、力丸満惠、林紗織、村上龍文、藤井績
    • Organizer
      平成21年度「砂田班」班会議
    • Place of Presentation
      東京
    • Year and Date
      2009-12-11
    • Related Report
      2011 Final Research Report
  • [Presentation] Introduction of wound-healing MRL-MpJ phenotype improves skeletal muscle pathology in mdx mouse2009

    • Author(s)
      Ohsawa Y, Fujino M, Okada T, Kuga A, Hayashi S, Rikimaru M, Sunada Y.
    • Organizer
      14th International Congress of The World Muscle Society
    • Place of Presentation
      Geneve, Switzerland
    • Year and Date
      2009-09-11
    • Related Report
      2011 Final Research Report
  • [Presentation] TGF-βタイプIセリンスレオニンキナーゼ受容体阻害剤による筋ジストロフィー治療法の開発(第2報)2009

    • Author(s)
      大澤裕、久我敦、林紗織、力丸満恵、村上龍文、砂田芳秀
    • Organizer
      第27回日本神経治療学会総会
    • Place of Presentation
      熊本
    • Year and Date
      2009-06-11
    • Related Report
      2011 Final Research Report
  • [Book] Fifty Years of Neuromuscular Disorder Research after Discovery of Creatine Kinase as a Diagnostic Marker of Muscular Dystrophy-Development and application of anti-myostatin therapy for muscular dystrophy-2011

    • Author(s)
      砂田芳秀
    • Publisher
      医学書院出版サービス,医学書院
    • Related Report
      2011 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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