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2013 Fiscal Year Final Research Report

Screening of muscle regenerative molecules for Duchenne muscular dystrophy

Research Project

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Project/Area Number 23591261
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurology
Research InstitutionKawasaki Medical School

Principal Investigator

OHSAWA Yutaka  川崎医科大学, 医学部, 講師 (80246511)

Co-Investigator(Kenkyū-buntansha) SUNADA Yoshihide  川崎医科大学, 医学部, 教授 (00240713)
MURAKAMI Tatsufumi  川崎医科大学, 医学部, 准教授 (30330591)
Project Period (FY) 2011 – 2013
Keywords筋ジストロフィー / 創傷治癒 / 再生医療
Research Abstract

The MRL mouse shows complete closure of ear punch wounds. However, genetic and molecular mechanisms underlying the accelerated wound healing have remained largely unknown. We have mated dystrophin-deficient mdx mice with MRL mice to generate and characterize MRL-introduced mdx mice. Compared to the mdx mice, the MRL-mdx mice showed increased myofiber size and centrally-nucleated myofiber number, but decreased fibrosis in the diaphragm. By comparing the gene expression profile in diaphragm between mdx and MRL-mdx mice, we found several candidate genes contributing to the MRL-originated muscle regeneration. Among them, two genes eventually accelerating myotube formation in cultured myoblasts. Our results suggest that the introduction of the MRL wound-healer accelerates muscle regeneration by reducing muscle fibrosis, thereby becoming a novel therapeutic option for the dystrophin-deficient muscular dystrophy.

  • Research Products

    (30 results)

All 2014 2013 2012 2011

All Journal Article (9 results) (of which Peer Reviewed: 9 results) Presentation (19 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 2 results)

  • [Journal Article] SLC25A13 gene analysis in citrin deficiency : sixteen novel mutations in East Asian patients, and the mutation distribution in a large pediatric cohort in China2013

    • Author(s)
      Song YZ, Zhang ZH, Lin WX, Zhao XJ, Deng M, Ma YL, Guo L, Chen FP, Long XL, He XL, Sunada Y, Soneda S, Nakatomi A, Dateki S, Ngu LH, Kobayashi K, Saheki T
    • Journal Title

      PLoS One

      Volume: 8(9) Pages: e74544

    • Peer Reviewed
  • [Journal Article] Local Applications of Myostatin-siRNA with Atelocollagen Increse Skeletal Muscle Mass and Recovery of Muscle Function2013

    • Author(s)
      Kawakami E, Kawai N, Kinouchi N, Mori H, Ohsawa Y, Ishimaru N, Sunada Y, Noji S, Tanaka E
    • Journal Title

      PLoS One

      Volume: 8(5) Pages: e64719

    • Peer Reviewed
  • [Journal Article] Modeling Alzheimer's Disease with iPSCs Reveals Stress Phenotypes Associated with Intracellular Aβand Differential Drug Responsiveness2013

    • Author(s)
      Kondo T, Asai M, Tsukita K, Kutoku Y, Ohsawa Y, Sunada Y, Imamura K, Egawa N, Yahata N, Okita K, Takahashi K, Asaka I, Aoi T, Watanabe A, Watanabe K, Kadoya C, Nakano R, Watanabe D, Maruyama K, Hori O, Hibino S, Choshi T, Nakahata T, Hioki H, Kaneko T, Naitoh M, Yoshikawa K, Yamawaki S, Suzuki S, Hata R, Ueno SI, Seki T, Kobayashi K, Toda T, Murakami K, Irie K, Klein WL, Mori H, Asada T, Takahashi R, Iwata N, Yamanaka S, Inoue H
    • Journal Title

      Cell Stem Cell

      Volume: 12(4) Pages: 487-496

    • Peer Reviewed
  • [Journal Article] Development of sensory neuropathy in streptozotocin-induced diabetic mice2012

    • Author(s)
      Murakami T, Iwanaga T, Ogawa Y, Fujita Y, Sato E, Yoshitomi H, Sunada Y, Nakamura A
    • Journal Title

      Brain and Behavior

      Volume: 3(1) Pages: 101-107

    • Peer Reviewed
  • [Journal Article] Taurine Ameliorates Impaired the Mitochondrial Function and Prevents Stroke-like Episodes in Patients with MELAS2012

    • Author(s)
      Rikimaru M, Ohsawa Y, Alexander M.Wolf, Nishimaki K, Ichimiya H, Kamimura N, Nishimatsu S, Ohta S, Sunada Y
    • Journal Title

      Internal medicine

      Volume: 51(24) Pages: 3351-3357

    • Peer Reviewed
  • [Journal Article] Muscle-specific overexpression of caveolin 3 causes muscle atrophy, but not muscular dystrophy2012

    • Author(s)
      Ohsawa Y, Fujino M, Nishimatsu S, Rikimaru M, Hayashi S, Sunada Y
    • Journal Title

      Neuromuscular Disorders

      Volume: 22(9-10) Pages: 834

    • Peer Reviewed
  • [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 S, Ishizaki M, Suga T, Fujino M, Murakami T, Uchino M, Tsuchida K, Noji S, Hinohara A, Shimizu T, Shimizu K, Sunada Y
    • Journal Title

      Laboratory Investigation

      Volume: 92(8) Pages: 1100-1114

    • Peer Reviewed
  • [Journal Article] Plasmid DNA Gene Therapy by Electroporation : Principles and Recent Advances2011

    • Author(s)
      Murakami T, Sunada Y
    • Journal Title

      Current Gene Therapy

      Volume: 11(6) Pages: 447-456

    • 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) Pages: 2975-2983

    • Peer Reviewed
  • [Presentation] Inverse regulation of myogenesis and adipogenesis by caveolin-3 through type I TGF-βreceptor kinase2013

    • Author(s)
      Ohsawa Y, Nishimatsu S, Fujino M, Hagiwara H, Hinohara A, Sunada Y
    • Organizer
      EMBO Workshop - Molecular Mechanisms of muscle growth and wasting in health and disease
    • Place of Presentation
      Ascona,Switzerland
    • Year and Date
      20130915-20
  • [Presentation] TGF-beta阻害低分子医薬による筋消耗性疾患とメタボリック症候群の治療戦略2013

    • Author(s)
      大澤裕
    • Organizer
      第31回日本神経治療学会総会
    • Place of Presentation
      東京
    • Year and Date
      2013-11-22
  • [Presentation] Taurine ameliorates mitochondrial dysfunction and prevents stroke-like episodes in patients with MELAS2013

    • Author(s)
      Sunada Y, Rikimaru M, Ohsawa Y, Murakami T, Nishimatsu S, Hagiwara H, Ohta S
    • Organizer
      XXI World Congress Of Neurology
    • Place of Presentation
      Vienna, Austria
    • Year and Date
      2013-09-22
  • [Presentation] TGF-betaシグナル制御による筋消耗性疾患治療法の開発2013

    • Author(s)
      大澤裕
    • Organizer
      第54回日本神経学会学術大会
    • Place of Presentation
      東京
    • Year and Date
      2013-05-31
  • [Presentation] ヒト異型トランスサイレチン遺伝子を発現する不死化シュワン培養細胞の確立2013

    • Author(s)
      村上龍文,三五一憲,渡部和彦,大澤裕,李正花,山村研一,砂田芳秀
    • Organizer
      第54回日本神経学会学術大会
    • Place of Presentation
      東京
    • Year and Date
      2013-05-30
  • [Presentation] 低分子TβRIキナーゼ阻害剤による骨格筋消耗性質患の薬物治療への展望2012

    • Author(s)
      大澤裕、力丸満惠、砂田芳秀
    • Place of Presentation
      福岡
    • Year and Date
      2012-11-30
  • [Presentation] 診療・治療の最前線4「筋ジストロフィーの分子治療」2012

    • Author(s)
      砂田芳秀
    • Place of Presentation
      福岡
    • Year and Date
      2012-11-29
  • [Presentation] ストレプトゾトシン誘発糖尿病マウスの感覚ニューロパチーの発現2012

    • Author(s)
      村上龍文,岩永崇志,小川芳尚,藤田吉明,佐藤英治,吉富博則,砂田芳秀,中村明弘
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋
    • Year and Date
      2012-09-20
  • [Presentation] Caveolin-3 controls satellite cells and myoblasts through type I TGF-beta receptor kinase2012

    • Author(s)
      Ohsawa Y, Nishimatsu S, Sunada Y
    • Organizer
      FASEB Science Research Conferences SKELETAL MUSCLE SATELLITE AND STEM CELLS
    • Place of Presentation
      Lucca,ITALY
    • Year and Date
      2012-08-16
  • [Presentation] Roles of the caveolin-3-transforming gowth factor-beta axis in skeletal myogenesis and muscle atrophy2012

    • Author(s)
      Ohsawa Y, Nishimatsu S, Sunada Y
    • Organizer
      DEVELOPMENT,FUNCTION AND REPAIR OF THE MUSCLE CELL Society for Muscle Biology
    • Place of Presentation
      New York,USA
    • Year and Date
      2012-06-07
  • [Presentation] ストレプトゾトシン誘発糖尿病マウスのニューロパチーの検討:小径線維障害について2012

    • Author(s)
      村上龍文,小川芳尚,岩永崇志,藤田吉明,佐藤英治,吉富博則,中村明弘,砂田芳秀
    • Organizer
      第53回日本神経学会学術大会
    • Place of Presentation
      東京
    • Year and Date
      2012-05-25
  • [Presentation] 直接リプログラミング戦略による筋ジストロフィーの再生療法2012

    • Author(s)
      大澤裕,力丸満惠,林紗織,村上龍文,砂田芳秀
    • Organizer
      第53回日本神経学会学術大会
    • Place of Presentation
      東京
    • Year and Date
      2012-05-24
  • [Presentation] Sarcolemmal nNOS prevents muscular wasting in a caveolin-3-deficient limb-girdle muscular dystrophy 1C model2011

    • Author(s)
      Ohsawa Y, Fujino M, Okada T, Nishimatsu S, Rikimaru M, Hayashi S, Sunada Y
    • Organizer
      NTERNATIONAL CONFERENCE ON MUSCLE WASTING 2011, MOLECULAR MECHANISMS OF MUSCLE GROWTH AND WASTING IN HEALTH AND DISEASE
    • Place of Presentation
      Switzerland
    • Year and Date
      20110918-23
  • [Presentation] Transthyretin gene expression in Schwann cells of peripheral nerves2011

    • Author(s)
      Murakami T, Ohsawa Y, Watabe K, Zhenghua L, Yamamura K, Sunada Y
    • Organizer
      第8回FAP国際シンポジウム
    • Place of Presentation
      熊本
    • Year and Date
      2011-11-19
  • [Presentation] ストレプトゾトシン誘発糖尿病マウスでのニューロパチー発現機序の検討:神経成熟・成長障害の関与について2011

    • Author(s)
      村上龍文,岩永崇志,小川芳尚,藤田吉明,佐藤英治,吉富博則,中村明弘,砂田芳秀
    • Organizer
      第22回日本末梢神経学会学術集会
    • Place of Presentation
      沖縄
    • Year and Date
      2011-09-02
  • [Presentation] 筋ジストロフィー研究の現状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
    • Year and Date
      2011-05-22
  • [Presentation] PIGF-2遺伝子治療はマウスの糖尿病性感覚ニューロパチーを改善させる2011

    • Author(s)
      村上龍文
    • Organizer
      第52回日本神経学会学術大会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-05-19
  • [Presentation] direct reprogrammingによる筋細胞の樹立と筋ジストロフィー治療への応用2011

    • Author(s)
      大澤裕
    • Organizer
      第52回日本神経学会学術大会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-05-19
  • [Presentation] 末梢神経系でのトランスサイレチン遺伝子発現の再検討2011

    • Author(s)
      村上龍文,大澤裕,渡部和彦,李生花,山村研一,砂田芳秀
    • Organizer
      第34回日本神経科学大会-こころの脳科学-
    • Place of Presentation
      横浜
    • Year and Date
      2011-05-17
  • [Patent(Industrial Property Rights)] マイオスタンチン阻害ペプチド2014

    • Inventor(s)
      大澤裕、砂田芳秀、林良雄、 他6名
    • Industrial Property Rights Holder
      学校法人川崎学園・学校法人東京薬科大学
    • Industrial Property Number
      PCT/JP2014/052345
    • Filing Date
      2014-01-31
    • Overseas
  • [Patent(Industrial Property Rights)] マイオスタンチン阻害ペプチド2013

    • Inventor(s)
      大澤裕、砂田芳秀、林良雄、 他6名
    • Industrial Property Rights Holder
      学校法人川崎学園・学校法人東京薬科大学
    • Industrial Property Number
      特願2013-17540
    • Filing Date
      2013-01-31
    • Overseas

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Published: 2015-07-16  

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