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Analysis of extracellular vesicles derived from microvascular endothelial cells: towards the development of treatment for cerebral white matter infarction

Research Project

Project/Area Number 17K10291
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Psychiatric science
Research InstitutionGunma University

Principal Investigator

Kurachi Masashi  群馬大学, 大学院医学系研究科, 助教 (20271546)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords血管内皮細胞 / 細胞外小胞 / エクソソーム / オリゴデンドロサイト前駆細胞 / 神経科学 / 再生医学 / 認知症 / 脳白質障害
Outline of Final Research Achievements

I found that fibronectin (FN) was abundant on the surface of extracellular vesicles derived from brain microvascular endothelial cells (MVEC-EVs) and that FN on EVs mediated their internalization into oligodendrocyte precursor cells (OPCs) by its binding to heparan sulfate proteoglycan (HSPG) on OPCs. OPC survival and proliferation promoted by EVs were attenuated by blocking the internalization of EVs into OPCs. Moreover, I also found that platelet-derived growth factor-B (PDGF-B) was on the surface of MVEC-EVs and that PDGF-B was tethered to the EV by HSPG. The neutralizing antibody against PDGF-B significantly reduced the promoting activity of MVEC-EVs on OPC proliferation, suggesting that PDGF-B on the surface of MVEC-EV promotes OPC proliferation.

Academic Significance and Societal Importance of the Research Achievements

微小血管内皮細胞由来細胞外小胞の表面にフィブロネクチン、血小板由来成長因子PDGF-Bが存在すること、小胞内にrno-miR-21-5pなどのマイクロRNAが含まれることを明らかにした。また、細胞外小胞表面のPDGF-BBがオリゴデンドロサイト前駆細胞の増殖を促進することを明らかにした。これらの知見は、運動機能や認知機能の障害に関わる白質病変の改善に向けた治療戦略の構築に有用であると考えられる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (19 results)

All 2020 2019 2018 2017

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (14 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Transplantation of iPS‐derived vascular endothelial cells improves white matter ischemic damage2020

    • Author(s)
      Xu Bin、Kurachi Masashi、Shimauchi‐Ohtaki Hiroya、Yoshimoto Yuhei、Ishizaki Yasuki
    • Journal Title

      Journal of Neurochemistry

      Volume: - Issue: 6 Pages: 759-771

    • DOI

      10.1111/jnc.14949

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The dynamics of revascularization after white matter infarction monitored in Flt1-tdsRed and Flk1-GFP mice2019

    • Author(s)
      Shimauchi-Ohtaki Hiroya、Kurachi Masashi、Naruse Masae、Shibasaki Koji、Sugio Shouta、Matsumoto Ken、Ema Masatsugu、Yoshimoto Yuhei、Ishizaki Yasuki
    • Journal Title

      Neuroscience Letters

      Volume: 692 Pages: 70-76

    • DOI

      10.1016/j.neulet.2018.10.057

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] X-ray irradiation induces disruption of the blood-brain barrier with localized changes in claudin-5 and activation of microglia in the mouse brain.2018

    • Author(s)
      Yoshida Y, Sejimo Y, Kurachi M, Ishizaki Y, Nakano T, Takahashi A.
    • Journal Title

      Neurochem Int.

      Volume: 印刷中 Pages: 199-206

    • DOI

      10.1016/j.neuint.2018.03.002

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] BMP4 signaling in NPCs upregulates Bcl-xL to promote their survival in the presence of FGF-22018

    • Author(s)
      Yamamoto Hanako、Kurachi Masashi、Naruse Masae、Shibasaki Koji、Ishizaki Yasuki
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 496 Issue: 2 Pages: 588-593

    • DOI

      10.1016/j.bbrc.2018.01.090

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Fibronectin on extracellular vesicles from microvascular endothelial cells is involved in the vesicle uptake into oligodendrocyte precursor cells2017

    • Author(s)
      Osawa Sho、Kurachi Masashi、Yamamoto Hanako、Yoshimoto Yuhei、Ishizaki Yasuki
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 488 Issue: 1 Pages: 232-238

    • DOI

      10.1016/j.bbrc.2017.05.049

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] Transplantation of iPS-derived vascular endothelial cells ameliorates white matter infarct2020

    • Author(s)
      Xu Bin, Kurachi Masashi, Shimauchi-Ohtaki Hiroya, Yoshimoto Yuhei, Ishizaki Yasuki
    • Organizer
      The 10th Conference of International Society of Radiation Neurobiology
    • Related Report
      2019 Annual Research Report
  • [Presentation] The dynamics of revascularization after white matter infarction monitored in Flt1-tdsRed and Flk1-GFP mice.2019

    • Author(s)
      Shimauchi-Ohtaki Hiroya, Kurachi Masashi, Naruse Masae, Shibasaki Koji, Sugio Shouta, Matsumoto Ken, Ema Masatsugu, Yoshimoto Yuhei, Ishizaki, Yasuki
    • Organizer
      The 29th International Symposium on Cerebral Blood Flow, Metabolism and Function
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A role for PDGF-B in the stimulatory effect of exosomes from cerebral microvascular endothelial cells on proliferation of oligodendrocyte precursor cells.2019

    • Author(s)
      Ishizaki Yasuki, Kurachi Masashi, Xu Bin, Matsuzaki Toshiyuki
    • Organizer
      XIV European Meeting on Glial Cells in Health and Disease
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Calpain/calpastatin system plays a role for control of NPC survival by via cleavage of Bax.2019

    • Author(s)
      Yamamoto Hanako, Kurachi Masashi, Shibasaki Koji, Naruse Masae, Ishizaki Yasuki
    • Organizer
      Neuro 2019 (第42回日本神経科学大会・第62回日本神経化学会大会)
    • Related Report
      2019 Annual Research Report
  • [Presentation] PDGF-B in the extracellular vesicles from brain microvascular endothelial cells promotes proliferation of oligodendrocyte precursor cells.2019

    • Author(s)
      Kurachi Masashi, Xu Bin, Osawa Sho, Matsuzaki Toshiyuki, Ishizaki Yasuki
    • Organizer
      Neuro 2019 (第42回日本神経科学大会・第62回日本神経化学会大会)
    • Related Report
      2019 Annual Research Report
  • [Presentation] Effect of transplantation of iPS-derived vascular endothelial cells on white matter infarct.2019

    • Author(s)
      Xu Bin, Kurachi Masashi, Shimauchi-Ohtaki Hiroya, Yoshimoto Yuhei, Ishizaki Yasuki
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Fibronectin on extracellular vesicles from microvascular endothelial cells plays a role for the vesicle uptake into oligodendrocyte precursor cells2019

    • Author(s)
      大澤 祥, 倉知 正, 山本華子, 好本裕平, 石崎泰樹
    • Organizer
      The 9th Conference of International Society of Radiation Neurobiology
    • Related Report
      2018 Research-status Report
  • [Presentation] FGF-2とBMP4シグナルによる神経幹細胞様細胞のアポトーシス抑制とBax制御2018

    • Author(s)
      山本華子, 倉知 正, 成瀬雅衣, 柴崎貢志, 石崎泰樹
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Effect of extracellular vesicles from X-ray irradiated glioblastoma cells on survival, proliferation and motility of oligodendrocyte precursor cells2018

    • Author(s)
      石崎泰樹, 倉知 正, 山口舞花, 山本華子, 吉田由香里, 大澤 祥, 行木信一, 高橋昭久
    • Organizer
      The 8th Conference of International Society of Radiation Neurobiology
    • Related Report
      2017 Research-status Report
  • [Presentation] X-ray irradiation induces disruption of the blood-brain barrier with localized changes in claudin-5 and activation of microglia in the mouse brain2018

    • Author(s)
      吉田由香里, 瀬下幸彦, 倉知 正, 石崎泰樹, 中野 隆史, 高橋昭久
    • Organizer
      The 8th Conference of International Society of Radiation Neurobiology
    • Related Report
      2017 Research-status Report
  • [Presentation] FGF-2とBMP4シグナルによるBaxを介したアポトーシスの制御2017

    • Author(s)
      山本華子, 倉知 正, 成瀬雅衣, 柴崎貢志, 石崎泰樹
    • Organizer
      第40回日本分子生物学会年会・第90回日本生化学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Fibronectin on the surface of microvascular endothelial cell-derived extracellular vesicles mediates their uptake into oligodendrocyte precursor cells2017

    • Author(s)
      大澤 祥, 倉知 正, 山本華子, 好本裕平, 石崎泰樹
    • Organizer
      第60回日本神経化学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Fibronectin on extracellular vesicles from microvascular endothelial cells mediates vesicle uptake into oligodendrocyte precurs2017

    • Author(s)
      大澤 祥, 倉知 正, 山本華子, 好本裕平, 石崎泰樹
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 正常脳組織における放射線急性障害の解析2017

    • Author(s)
      吉田由香里, 瀬下幸彦, 倉知 正, 石崎泰樹, 中野隆史, 高橋昭久
    • Organizer
      第55回日本放射線腫瘍学会生物部会学術大会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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