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Elucidating the mechanism of abnormal protein aggregation in sporadic inclusion body myositis by single molecule nanoimaging

Research Project

Project/Area Number 18K19505
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 52:General internal medicine and related fields
Research InstitutionTohoku University

Principal Investigator

Aoki Masashi  東北大学, 医学系研究科, 教授 (70302148)

Co-Investigator(Kenkyū-buntansha) 割田 仁  東北大学, 大学病院, 助教 (30400245)
鈴木 直輝  東北大学, 医学系研究科, 非常勤講師 (70451599)
Project Period (FY) 2018-06-29 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords封入体筋炎 / RNAシークエンス / 電気収縮培養 / TDP-43 / プロテアソーム / 骨格筋生物学 / 電気収縮 / 細胞内凝集体 / 筋収縮 / 筋芽細胞
Outline of Final Research Achievements

In this study, myoblasts were harvested from sporadic inclusion body myositis (sIBM) patients during muscle biopsy, and a total of six lines were stocked during these two years. Cellular stress was applied to human skeletal muscle using electro-pulse-constriction-culture-system (EPS) which reproduces long-lasting muscle contraction. Analysis was performed by RNA sequencing using cells before and after contraction stress. The characteristics of the co-culture system (EPS culture) were reported in an international journal. In addition, TDP-43, which is a component of the aggregates, is labeled by single-molecule nanoimaging, and the presence or absence of aggregate formation before and after EPS culture was evaluated. Furthermore, analysis of the myoblast specific proteasome deficient mouse revealed that p53 is important for the maintenance of myoblasts pool.

Academic Significance and Societal Importance of the Research Achievements

学術的には2報の論文を国際誌に掲載することができた。一つは封入体筋炎の病態に関与すると考えられる蛋白分解系であるプロテアソームの骨格筋における役割をStem Cell Reports誌に、もう一つは本研究課題の主要評価系である電気収縮培養のシステムとしての有用性についてSciRep誌に、それぞれ報告した。今後、本研究を発展させるうえで、いずれも重要な論文である。前者はプレスリリースも行い、社会的にも骨格筋生物学研究の意義について広く周知することができた。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (5 results)

All 2020 2019 2018

All Journal Article (5 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 5 results,  Open Access: 5 results)

  • [Journal Article] AMPK Complex Activation Promotes Sarcolemmal Repair in Dysferlinopathy2020

    • Author(s)
      Ono Hiroya、Suzuki Naoki、Kanno Shin-ichiro、Kawahara Genri、Izumi Rumiko、Takahashi Toshiaki、Kitajima Yasuo、Osana Shion、Nakamura Naoko、Akiyama Tetsuya、Ikeda Kensuke、Shijo Tomomi、Mitsuzawa Shio、Nagatomi Ryoichi、Araki Nobukazu、Yasui Akira、Warita Hitoshi、Hayashi Yukiko K.、Miyake Katsuya、Aoki Masashi
    • Journal Title

      Molecular Therapy

      Volume: 28 Issue: 4 Pages: 1133-1153

    • DOI

      10.1016/j.ymthe.2020.02.006

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The updated retrospective questionnaire study of sporadic inclusion body myositis in Japan2019

    • Author(s)
      Suzuki Naoki、Mori-Yoshimura Madoka、Yamashita Satoshi、…Nishino Ichizo、Aoki Masashi
    • Journal Title

      Orphanet Journal of Rare Diseases

      Volume: 14 Issue: 1 Pages: 155-163

    • DOI

      10.1186/s13023-019-1122-5

    • NAID

      120006956841

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Safety and efficacy of intravenous bimagrumab in inclusion body myositis (RESILIENT): a randomised, double-blind, placebo-controlled phase 2b trial2019

    • Author(s)
      Hanna Michael G、Badrising Umesh A、Benveniste Olivier、Lloyd Thomas E、Needham Merrilee、Chinoy Hector、Aoki Masashi、...Amato Anthony A
    • Journal Title

      The Lancet Neurology

      Volume: 18 Issue: 9 Pages: 834-844

    • DOI

      10.1016/s1474-4422(19)30200-5

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vitro exercise model using contractile human and mouse hybrid myotubes2019

    • Author(s)
      Chen Weijian、Nyasha Mazvita R.、Koide Masashi、Tsuchiya Masahiro、Suzuki Naoki、Hagiwara Yoshihiro、Aoki Masashi、Kanzaki Makoto
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 11914-11914

    • DOI

      10.1038/s41598-019-48316-9

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Ubiquitin-Proteasome System Is Indispensable for the Maintenance of Muscle Stem Cells2018

    • Author(s)
      Kitajima Yasuo、Suzuki Naoki、Nunomiya Aki、Osana Shion、Yoshioka Kiyoshi、Tashiro Yoshitaka、Takahashi Ryosuke、Ono Yusuke、Aoki Masashi、Nagatomi Ryoichi
    • Journal Title

      Stem Cell Reports

      Volume: 11 Issue: 6 Pages: 1523-1538

    • DOI

      10.1016/j.stemcr.2018.10.009

    • NAID

      120007006241

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research

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Published: 2018-07-25   Modified: 2021-02-19  

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