The elucidation of molecular mechanisms of capillary dysfunction with dermatomyositis.

• Project/Area Number: 18K07527
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Yamaguchi University
• Principal Investigator: Sano Yasuteru 山口大学, 大学院医学系研究科, 助教 (20379978)
• 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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 皮膚筋炎 / タイトジャンクション / 微小血管内皮細胞 / ペリサイト / 骨格筋微小血管

Outline of Final Research Achievements

Dermatomyositis (DM) is an immune-mediated disorder that most prominently involves muscle and skin. The loss of tight junction (TJ) of some remaining microvasculature is a hallmark of DM. Firstly, we demonstrated the possibility that sera from DM patients bring apoptosis of endothelium derived from endomysial capillaries. Then, we disclosed that GDNF and bFGF released from human skeletal muscle pericyte cell (HSMPCT) line increase the barrier function of human skeletal muscle microvascular endothelial cell line, TSM15. In addition, we also demonstrated that activated vitamin D strengthen the barrier function of TSM15. These results indicate that bFGF and GDNF, as well as activated vitamin D, might ameliorate the pathophysiology of DM via restoring the fragile barrier of endomysial endothelium.

Academic Significance and Societal Importance of the Research Achievements

本研究成果は，皮膚筋炎の新たな治療法開発へと発展する可能性を秘めている．また，我々が樹立したヒト骨格筋内皮細胞株とペリサイト株は骨格筋微小血管の生理学の理解に役立つだけでなくデュシェンヌ型筋ジストロフィーなど骨格筋微小血管に障害がみられる筋疾患の病態理解に役立つものと考えられる．

Research Products

• [Presentation] Activated vitamin D increases the barrier function of the endomysial endothelium (2020)
  • Author(s): Yasuteru Sano, Eri Ishiguchi, Toshihiko Maeda, Fumitaka Shimizu, Yukio Takeshita, Masaya Honda, and Takashi Kanda
  • Organizer: 第61回日本神経学会学術大会
• [Presentation] The role of pericytes for the barrier function of the endomysial endothelium (2019)
  • Author(s): Yasuteru Sano, Eri Ishiguchi, Fumitaka Shimizu, Masatoshi Omoto, Toshihiko Maeda,
  • Organizer: 第60回日本神経学会学術大会 大阪 2019年6月1日
• [Presentation] 活性化ビタミンDの骨格筋微小血管内皮細胞への効果に関する検討 (2019)
  • Author(s): 佐野泰照，清水文崇，前田敏彦，本田真也，竹下幸男，古賀道明，神田隆
  • Organizer: 第31回日本神経免疫学会学術集会
• [Presentation] Establishment of a new human skeletal muscle microvascular endothelial cell line (2018)
  • Author(s): Yasuteru Sano, Hironori Sano, Fumitaka Shimizu, Toshihiko Maeda, Masatoshi Omoto, and Takashi Kanda
  • Organizer: 日本筋学会第4回学術集会
  • Int'l Joint Research
• [Presentation] 骨格筋微小血管のバリア機能に対するペリサイトの役割 (2018)
  • Author(s): 佐野泰照，石口絵梨，清水文崇，尾本雅俊，竹下幸男，前田敏彦，神田隆
  • Organizer: 第30回日本神経免疫学会学術集会