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Role of the VEGF/VEGFR2 signaling in vascular stability

Research Project

Project/Area Number 15K15089
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Pathological medical chemistry
Research InstitutionKeio University

Principal Investigator

Kubota Yoshiaki  慶應義塾大学, 医学部(信濃町), 教授 (50348687)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords血管 / 血管新生 / VEGF / VEGFR2 / 網膜 / 発現制御 / 発生・分化 / 循環器・高血圧
Outline of Final Research Achievements

Blood vessels are distributed throughout the body during development. This developmental process depends on the signaling of vascular endothelial growth factor (VEGF) and its main receptor, VEGFR2. However, the precise role of VEGF on vascular endothelial cells, in particular the role in the maintenance of their stability is not clear. In this study, we generated tamoxifen-inducible endothelial VEGFR2 knockout mice (Cdh5-BAC-CreERT2+;Vegfr2flox./flox) and morphologically analyzed the retina of the mutant mice at a single cell level. We found not only abrogation of the formation of new vessels but also the striking regression of established ones. This phenotype was mostly recapitulated by neuron-specific VEGF knockout mice (Chx10-Cre+Vegfaflox/flox). Overall our study suggests that the VEGF/VEGFR2 signaling positively regulates the stability of established blood vessels.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (17 results)

All 2016 2015 Other

All Int'l Joint Research (4 results) Journal Article (4 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 4 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) (of which Int'l Joint Research: 6 results,  Invited: 8 results) Remarks (1 results)

  • [Int'l Joint Research] Korea Advanced Institutes of Technology(韓国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] Soochow University(中国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] Harvard University(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] University of Illinois at Chicago(米国)

    • Related Report
      2015 Research-status Report
  • [Journal Article] Developmental regression of hyaloid vasculature is triggered by neurons.2016

    • Author(s)
      Yoshikawa Y, Yamada T, Tai-Nagara I, Okabe K, Kitagawa Y, Ema M and Kubota Y
    • Journal Title

      The Journal of Experimental Medicine

      Volume: 213 Issue: 7 Pages: 1175-1183

    • DOI

      10.1084/jem.20151966

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] SoxF Transcription Factors Are Positive Feedback Regulators of VEGF Signaling.2016

    • Author(s)
      Kim K, Kim IK, Yang JM, Lee E, Koh BI, Song S, Park J, Lee S, Choi C, Kim JW, Kubota Y, Koh GY and Kim I
    • Journal Title

      Circulation Research

      Volume: 119 Issue: 7 Pages: 839-852

    • DOI

      10.1161/circresaha.116.308483

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] VEGFR3 does not sustain retinal angiogenesis without VEGFR2.2015

    • Author(s)
      Zarkada G, Heinolainen K, Makinen T, Kubota Y, Alitalo K
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 112 Issue: 3 Pages: 761-766

    • DOI

      10.1073/pnas.1423278112

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Perilipin+ embryonic preadipocytes actively proliferate along growing vasculatures for adipose expansion.2015

    • Author(s)
      Hong KY, Bae H, Park I, Park DY, Kim KH, Kubota Y, Cho ES, Kim H, Adams RH, Yoo OJ, Koh GY
    • Journal Title

      Development

      Volume: 142 Issue: 15 Pages: 2623-2632

    • DOI

      10.1242/dev.125336

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Cell-cell interactions for retinal vascular development2016

    • Author(s)
      Yoshiaki Kubota
    • Organizer
      The 14th Korea-Japan Joint Symposium on Vascular Biology
    • Place of Presentation
      長崎ブリックホール(長崎県長崎市)
    • Year and Date
      2016-12-08
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Neuro-vascular crosstalk in the developing retina2016

    • Author(s)
      Yoshiaki Kubota
    • Organizer
      19th International Vascular Biology Meeting
    • Place of Presentation
      Sheraton Boston Hotel (Boston)
    • Year and Date
      2016-10-31
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Neuro-vascular crosstalk in the central nervous system2016

    • Author(s)
      久保田義顕
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      東北大学川内北キャンパス(宮城県仙台市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Vascular development and diseases.2015

    • Author(s)
      久保田義顕
    • Organizer
      9th International Cell Therapy Conference.
    • Place of Presentation
      ソウル(韓国)
    • Year and Date
      2015-10-22
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Neuro-vascular crosstalk in the developing retina2015

    • Author(s)
      久保田義顕
    • Organizer
      Lecture in Natinal University of Singapore.
    • Place of Presentation
      シンガポール(シンガポール)
    • Year and Date
      2015-10-07
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] VEGF/VEGFR2 signaling in retinal vascular development.2015

    • Author(s)
      久保田義顕
    • Organizer
      10th World Congress for Microcirculation.
    • Place of Presentation
      京都国際会議場(京都府京都市)
    • Year and Date
      2015-09-25
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Neuro-vascular interaction in the developing retina2015

    • Author(s)
      久保田義顕
    • Organizer
      第58回日本神経化学会大会
    • Place of Presentation
      大宮ソニックシティ―(埼玉県さいたま市)
    • Year and Date
      2015-09-11
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] マクロファージによる血管新生制御2015

    • Author(s)
      久保田義顕
    • Organizer
      第36回炎症再生医学会
    • Place of Presentation
      虎ノ門ヒルズ(東京都港区)
    • Year and Date
      2015-07-21
    • Related Report
      2015 Research-status Report
    • Invited
  • [Remarks] 研究室ホームページ

    • URL

      http://www.keiovascular.com/

    • Related Report
      2016 Annual Research Report 2015 Research-status Report

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Published: 2015-04-16   Modified: 2022-02-16  

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