• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Mechanism of acrolein generation in diabetic retinopathy

Research Project

Project/Area Number 17K11442
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Ophthalmology
Research InstitutionHokkaido University

Principal Investigator

Murata Miyuki  北海道大学, 医学研究院, 特任助教 (50423752)

Co-Investigator(Kenkyū-buntansha) 野田 航介  北海道大学, 医学研究院, 准教授 (90296666)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords眼細胞生物学 / 糖尿病網膜症 / アクロレイン / 酸化ストレス / VAP-1
Outline of Final Research Achievements

Vascular adhesion protein-1 (VAP-1) expresses in vascular endothelial cells and involved in inflammation as a leukocyte adhesion molecule. In addition to its role as an adhesion molecule, VAP-1 also has enzymatic activity as an amine oxidase. Acrolein is a highly reactive unsaturated aldehyde and is included in cigarettes and so on as an exogenous pollutant. Recently it has been shown that acrolein is also produced endogenously as a consequence of polyamine oxidation. We found that the levels of the acrolein-conjugated protein are elevated in the vitreous fluid of patients with diabetic retinopathy (DR). VAP-1 protein levels are also elevated in the vitreous fluid of DR patients and correlated with acrolein-conjugated protein levels. In this study, we showed that VAP-1 generates acrolein by oxidizing the spermine, a kind of polyamine.

Academic Significance and Societal Importance of the Research Achievements

糖尿病網膜症の病態形成には、炎症と酸化ストレスの亢進が重要な役割を果たす。本研究では、白血球接着分子として炎症を促進する分子であるVAP-1が、糖尿病網膜症患者の硝子体中で増加するスペルミンを基質として不飽和アルデヒドであるアクロレインを生成し、酸化ストレスの亢進にも関与することを明らかにした。本研究により糖尿病網膜症の病態形成の新たなメカニズムが明らかになり、新規治療法の開発につながる重要な知見を得ることができた。

Report

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

    (12 results)

All 2019 2018 2017

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (8 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Unsaturated Aldehyde Acrolein Promotes Retinal Glial Cell Migration2019

    • Author(s)
      Murata Miyuki、Noda Kousuke、Yoshida Shiho、Saito Michiyuki、Fujiya Akio、Kanda Atsuhiro、Ishida Susumu
    • Journal Title

      Investigative Opthalmology & Visual Science

      Volume: 60 Issue: 13 Pages: 4425-4435

    • DOI

      10.1167/iovs.19-27346

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Proteolytic cleavage of vascular adhesion protein-1 induced by vascular endothelial growth factor in retinal capillary endothelial cells2018

    • Author(s)
      Yoshida Shiho、Murata Miyuki、Noda Kousuke、Matsuda Takashi、Saito Michiyuki、Saito Wataru、Kanda Atsuhiro、Ishida Susumu
    • Journal Title

      Jpn J Ophthalmol.

      Volume: 62 Issue: 2 Pages: 256-264

    • DOI

      10.1007/s10384-017-0555-4

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vascular Adhesion Protein-1 Blockade Suppresses Ocular Inflammation After Retinal Laser Photocoagulation in Mice2017

    • Author(s)
      Matsuda Takashi、Noda Kousuke、Murata Miyuki、Kawasaki Akiko、Kanda Atsuhiro、Mashima Yukihiko、Ishida Susumu
    • Journal Title

      Invest Ophthalmol Vis Sci

      Volume: 58 Issue: 7 Pages: 3254-3261

    • DOI

      10.1167/iovs.17-21555

    • NAID

      120006337769

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Soluble Vascular Adhesion Protein-1 Mediates Spermine Oxidation as Semicarbazide-Sensitive Amine Oxidase: Possible Role in Proliferative Diabetic Retinopathy2017

    • Author(s)
      Murata Miyuki、Noda Kousuke、Kawasaki Akiko、Yoshida Shiho、Dong Yoko、Saito Michiyuki、Dong Zhenyu、Ando Ryo、Mori Shohei、Saito Wataru、Kanda Atsuhiro、Ishida Susumu
    • Journal Title

      Curr Eye Res

      Volume: 42 Issue: 12 Pages: 1674-1683

    • DOI

      10.1080/02713683.2017.1359847

    • NAID

      120006540056

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Hypoxia inducible factor-1 regulates spermine oxidase leading to acrolein generation in Muller Glial cells2019

    • Author(s)
      Wu D, Noda K, Murata M, Liu Y, Kanda A and Ishida S.
    • Organizer
      Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Spontaneously Diabetic Torii fatty ラット網膜における炎症性サイトカインの発現解析2019

    • Author(s)
      菊地香澄、野田航介、村田美幸、神田敦宏、加瀬 諭、影山 靖、篠原雅巳、笹瀬智彦、石田 晋
    • Organizer
      第25回日本糖尿病眼学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Spontaneously Diabetic Torii fatty ラットにおける糖尿病白内障の検討2019

    • Author(s)
      菊地香澄、野田航介、村田美幸、田川義晃、神田敦宏、加瀬 諭、影山 靖、篠原雅巳、笹瀬智彦、石田 晋
    • Organizer
      第123回日本眼科学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Hypoxia aggravates acrolein generation via HIF-1/SMOX pathway in glial cells2019

    • Author(s)
      Wu D, Murata M, Noda K, Liu Y, Kanda A, Ishida S.
    • Organizer
      第123回日本眼科学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 網膜色素上皮細胞における胎盤成長因子のアポトーシス抑制効果2018

    • Author(s)
      村田美幸、野田航介、長谷敬太郎、神田敦宏、石田 晋
    • Organizer
      第57回日本網膜硝子体学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 増殖糖尿病網膜症患者の硝子体中アクロレイン結合蛋白とCXCL1濃度2018

    • Author(s)
      藤谷顕雄、野田航介、村田美幸、神田敦宏、石田 晋
    • Organizer
      第72回日本臨床眼科学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 網膜グリア細胞の遊走能に対するアクロレインの作用2018

    • Author(s)
      村田美幸
    • Organizer
      第22回眼科分子生物学研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] Accumulation of acrolein-conjugated protein in the vitreous fluid of proliferative diabetic retinopathy2017

    • Author(s)
      Noda K, Murata M, Saito W, Kanda A, Ishida S
    • Organizer
      Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi