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Regulation of angiogenesis by a novel VEGF receptor binding protein

Research Project

Project/Area Number 16K08600
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General medical chemistry
Research InstitutionAichi Medical University

Principal Investigator

Hayashi Hisaki  愛知医科大学, 医学部, 講師 (30533715)

Co-Investigator(Kenkyū-buntansha) 中原 努  北里大学, 薬学部, 教授 (10296519)
Research Collaborator Zako Masahiro  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords加齢黄斑変性 / 血管新生 / 脈絡膜 / G蛋白活性調節因子 / VEGF / 血管内皮増殖因子 / G蛋白調節因子 / 脈絡膜血管新生 / G蛋白 / G protein
Outline of Final Research Achievements

Vascular endothelial cell growth factor (VEGF) is essential for the development and progression of age-related macular degeneration (AMD), and VEGF signaling molecules are effective targets for the treatment of AMD. I have recently reported that activator of G-protein signaling 8 (AGS8) is a novel VEGF receptor-binding protein and is involved in VEGF-induced angiogenesis in cultured endothelial cells (EC); however, the role of AGS8 in CNV is not yet understood. This study aimed to explore the role of AGS8 in CNV in cultured cells, explanted choroid tissue, and laser-induced CNV in a mouse AMD model. Here, I finally reached my conclusion that AGS8 is a possible novel therapeutic target molecule for CNV in AMD.

Academic Significance and Societal Importance of the Research Achievements

失明原因ともなる加齢黄斑変性において脈絡膜血管新生の抑制が治療の鍵となるとされている。実際に現在ではVEGFを分子標的とした抗血管新生療法が行われているところであるが、VEGFは全身の血管に発現しており、抗VEGF療法では種々の副作用が報告されている。本研究において、加齢黄斑変性のモデルマウスでは、VEGF受容体結合分子であるAGS8は脈絡膜内皮細胞の新生血管部位にのみ限定的に発現しており、その発現抑制が効果的にVEGFシグナルおよび脈絡膜血管新生を抑制することが明らかになった。そのため、AGS8は加齢黄斑変性治療においては副作用の少ない特異的な新しい分子標的になりうる可能性が考えらえる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (16 results)

All 2019 2018 2017 2016

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (10 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results)

  • [Journal Article] Activator of G-protein signaling 8 is involved in VEGF-induced choroidal neovascularization2019

    • Author(s)
      Hayashi H, Mamun AA, Takeyama M, Yamamura A, Zako M, Yagasaki R, Nakahara T, Kamei M, Sato M
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 1560-1560

    • DOI

      10.1038/s41598-018-38067-4

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] VEGFR-3 signaling is regulated by a G-protein activator, activator of G-protein signaling 8, in lymphatic endothelial cells2018

    • Author(s)
      Sakima Miho、Hayashi Hisaki、Mamun Abdullah Al、Sato Motohiko
    • Journal Title

      Experimental Cell Research

      Volume: 未定 Issue: 1 Pages: 13-23

    • DOI

      10.1016/j.yexcr.2018.04.007

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Activator of G-protein signaling 8 is involved in VEGF-mediated signal processing in angiogenesis2016

    • Author(s)
      Hayashi H, Mamun AA, Sakima M, Sato M
    • Journal Title

      Journal of Cell Science

      Volume: 129 Issue: 6 Pages: 1210-1222

    • DOI

      10.1242/jcs.181883

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] High oxygen modifies vasodilator effect of cysteine via enhanced oxidative stress and thromboxane production in the rat mesenteric artery.2016

    • Author(s)
      Yasuda Y, Feng GG, Li J, Nakamura E, Hayashi H, Sato M, Fujiwara Y, Kinoshita H.
    • Journal Title

      Pflugers Arch.

      Volume: 468 Issue: 9 Pages: 1555-1564

    • DOI

      10.1007/s00424-016-1857-y

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Sevoflurane inhalation accelerates the long-term memory consolidation via small GTPase overexpression in the hippocampus of mice in adlescence.2016

    • Author(s)
      Nakamura E, Kinoshita H, Feng GG, Hayashi H, Satomoto M, Fujiwara Y.
    • Journal Title

      PloS One.

      Volume: 11 Issue: 9 Pages: e0163151-e0163151

    • DOI

      10.1371/journal.pone.0163151

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Adenosine triphosphate is a critical determinant for VEGFR signal during hypoxia.2016

    • Author(s)
      Mamun AA, Hayashi H, Sakima M, Sato Motohiko
    • Journal Title

      Am J Physiol Cell Physiol

      Volume: 311 Issue: 6 Pages: C985-C995

    • DOI

      10.1152/ajpcell.00145.2016

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Role of activator of G-protein signaling (AGS) 8 in vascular development and choroidal neovascularization.2019

    • Author(s)
      Hisaki Hayashi
    • Organizer
      The 9th FAOPS Congress
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 脈絡膜血管新生におけるG蛋白活性調節因子の機能2018

    • Author(s)
      林寿来 Mamun Abdulla Al 佐喜眞未帆 武山正行 雑喉正泰 矢ヶ崎莉菜 中原努 瓶井資弘 佐藤元彦
    • Organizer
      日本分子生物学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Activator of G-protein signaling 8 is involved in VEGF-induced choroidal angiogenesis2017

    • Author(s)
      Hisaki Hayashi, Abdullah Al Mamun, Miho Sakima, Masayuki Takeyama, Masahiro Zako, Rina Yagasaki, Tsutomu Nakahara, Motohiko Sato
    • Organizer
      Experimental Biology 2017
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2017-04-22
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Activator of G-protein signaling 8 is involved in VEGF-induced choroidal angiogenesis2017

    • Author(s)
      G-protein. Hisaki Hayashi, Abdullah Al Mamun, Miho Sakima, Masayuki Takeyama, Masahiro Zako, Rina Yagasaki, Tsutomu Nakahara, Motohiko Sato
    • Organizer
      The 93rd Annual Meeting of the Physiological Society of Japan
    • Place of Presentation
      浜松市
    • Year and Date
      2017-03-28
    • Related Report
      2016 Research-status Report
  • [Presentation] Inhibition of choroidal angiogenesis by targeting a regulatory protein for heterotrimeric G-protein2017

    • Author(s)
      Hisaki Hayashi, Abdullah Al Mamun, Miho Sakima, Masayuki Takeyama, Masahiro Zako, Rina Yagasaki, Tsutomu Nakahara, Motohiko Sato
    • Organizer
      The 90th Annual Meeting of the Japanese Pharmacological Society
    • Place of Presentation
      長崎市
    • Year and Date
      2017-03-15
    • Related Report
      2016 Research-status Report
  • [Presentation] Activator of G-protein signaling 8 is involved in VEGF-induced choroidal angiogenesis.2017

    • Author(s)
      Hisaki Hayashi, Masayuki Takeyama, Rina Yagasaki, Abdullah Al Mamun, Masahiro Zako, Tsutomu Nakahara, Motohiko Sato
    • Organizer
      Experimental Biology 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 脈絡膜血管新生におけるAGS8の意義2017

    • Author(s)
      林 寿来、Mamun Abdullah Al、佐喜眞 未帆、山村 彩、武山 正行、雑喉 正泰、 矢ヶ崎 莉菜、中原 努、瓶井 資弘、佐藤 元彦
    • Organizer
      日本病態生理学会
    • Related Report
      2017 Research-status Report
  • [Presentation] G蛋白活性調節因子による脈絡膜血管新生の制御2017

    • Author(s)
      林寿来 Mamun Abdulla Al 佐喜眞未帆 武山正行 雑喉正泰 矢ヶ崎莉菜 中原努 瓶井資弘 佐藤元彦
    • Organizer
      中部生理学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Gタンパク活性調節因子AGS8は脈絡膜血管新生を制御する2016

    • Author(s)
      林寿来, Abudollah Al Mamun, 佐喜眞未帆, 佐藤元彦
    • Organizer
      第63回中部日本生理学会
    • Place of Presentation
      岡崎市
    • Year and Date
      2016-11-03
    • Related Report
      2016 Research-status Report
  • [Presentation] The role of activator of G-protein 8 in choroidal vascular formation2016

    • Author(s)
      Hisaki Hayashi, Mamun Abudulla Al, Miho Sakima, Rina Yagasaki, Tsutomu Nakahara, Motohiko Sato
    • Organizer
      新血管膜輸送研究会2016
    • Place of Presentation
      福岡市
    • Year and Date
      2016-10-24
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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