Study on dystrophin Dp71 to regulate satellite cell division

• Project/Area Number: 18K07861
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Kobe Gakuin University
• Principal Investigator: Matsuo Masafumi 神戸学院大学, 総合リハビリテーション学部, 特命教授 (10157266)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: ジストロフィンDp71 / 衛生細胞 / Duchenne型筋ジストロフィー / 衛星細胞

Outline of Final Research Achievements

In order to clarify a role of Dp71 in the satellite cell proliferation, Dp71 mRNA in human satellite cells was analyzed by reverse-transcription PCR amplification. The full―length of Dp71 from exon G1 to 79 was PCR amplified as a clear band. Notably, sequencing of the product revealed that the product deleted exons 71 and 78, thereby encoding Dp71ab. Dp71ab was a sole isoform of Dp71 in satellite cells. Dp71 and Dp71ab expression plasmids were transfected into huma immortalized myoblasts and their proliferation was analyzed. Dp71 expression had no effect on cell proliferation. Remarkably, Dp71ab enhanced cell proliferation, significantly. It was concluded that Dp71ab is the molecule that regulates myoblast proliferation

Academic Significance and Societal Importance of the Research Achievements

筋衛星細胞は、数多くのDp71アイソフォームの中でDp71abのみを発現する極めて特徴的な細胞であることを明らかにした。また、筋芽細胞増殖作用解析において、Dp71が全く作用しなかったに対して、Dp71abは筋芽細胞増殖作用を発揮した。これは、Dp71が細胞増殖因子であるとのこれまでの説と大きく異なるもので、この作用が筋芽細胞特異的なのか、一般的な細胞増殖作用因子であるのか今後検討が必要である。Dp71abがin vivoでも筋細胞増殖作用を発揮し、Duchenne型筋ジストロフィーなどの筋萎縮疾患に対する治療の新たな分子となると大きく期待される。

Research Products

• [Journal Article] Dystrophin Dp71ab is monoclonally expressed in human satellite cells and enhances proliferation of myoblast cells (2020)
  • Author(s): Manal Farea, Abdul Qawee Mahyoob Rani, Kazuhiro Maeta, Hisahide Nishio, Masafumi Matsuo
  • Journal Title: Sci Rep Volume: 10 Issue: 1 Pages: 17123-17123
  • DOI: 10.1038/s41598-020-74157-y
  • Peer Reviewed / Open Access
• [Journal Article] Skipping of an exon with a nonsense mutation in the DMD gene is induced by the conversion of a splicing enhancer to a splicing silencer. (2019)
  • Author(s): Zhu Y, Deng H, Chen X, Li H, Yang C, Li S, Pan X, Tian S, Feng S, Tan X, Matsuo M, Zhang Z
  • Journal Title: Hum Genet Volume: 138 Issue: 7 Pages: 771-785
  • DOI: 10.1007/s00439-019-02036-2
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Identification of the shortest splice variant of Dp71, together with five known variants, in glioblastoma cells (2018)
  • Author(s): Abdul Q Rani, Farea M, Maeta K, Kawaguchi T, Awano H, Nagai M, Nishio H, Matsuo M
  • Journal Title: Biochem Biophy Res Commun Volume: 508 Issue: 2 Pages: 640-645
  • DOI: 10.1016/j.bbrc.2018.11.168
  • Peer Reviewed / Open Access