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RhoJ-mediated regulation of endothelial cell movements and vascular patterning

Research Project

Project/Area Number 25293078
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Pathological medical chemistry
Research InstitutionNagoya City University (2014-2015)
Kobe University (2013)

Principal Investigator

Uemura Akiyoshi  名古屋市立大学, 医学(系)研究科(研究院), 教授 (30373278)

Co-Investigator(Renkei-kenkyūsha) FUKUSHIMA Yoko  大阪大学, 大学院医学系研究科, 助教 (70647031)
MOCHIZUKI Naoki  独立行政法人国立循環器病研究センター, 細胞生物学部, 部長 (30311426)
NISHIYAMA Koichi  熊本大学, 国際先端医学研究機構, 特任准教授 (80398221)
MIURA Takashi  九州大学, 大学院医学研究院, 教授 (10324617)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2015: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2014: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2013: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
KeywordsRhoJ / VEGF / Sema3E / 血管新生 / 内皮細胞 / シグナル伝達 / 網膜 / 腫瘍 / 血管内皮細胞 / VEGFR2 / PlexinD1 / 腫瘍血管新生
Outline of Final Research Achievements

In newly formed blood vessels, migratory behaviors of angiogenic endothelial cells (ECs) are controlled by various attractive and repulsive signals, including vascular endothelial growth factor (VEGF) and semaphorin 3E (Sema3E). However, it remains unclear how individual ECs determine their migratory directions by integrating these extrinsic signals. In this research program, we discovered that a small GTPase RhoJ regulates directional EC movements by mediating intracellular signals downstream of both VEGF and Sema3E. We further identified that RhoJ modulates vascular patterning in developing retinas as well as in oxygen-induced retinopathy. Together, our present results will contribute to the understanding of molecular and cellular mechanisms underlying morphogenetic patterning, not only in vasculature but also in neural networks in which axonal guidance is cooperatively navigated by attractive and repulsive cues.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (28 results)

All 2016 2015 2014 2013 Other

All Int'l Joint Research (3 results) Journal Article (10 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 7 results,  Open Access: 1 results) Presentation (14 results) (of which Invited: 12 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Int'l Joint Research] German Cancer Research Center/Technische Universitat Dresden(ドイツ)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] CNIC(スペイン)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] KAIST(韓国)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Sequential Notch activation regulates ventricular chamber development.2016

    • Author(s)
      D'Amato G, Luxan G, del Monte-Nieto G, Martinez-Poveda B, Torroja C, Walter W, Bochter MS, Benedito R, Cole S, Martinez F, Hadjantonakis AK, Uemura A, Jimenez-Borreguero LJ, de la Pompa JL.
    • Journal Title

      Nat Cell Biol.

      Volume: 18 Issue: 1 Pages: 7-20

    • DOI

      10.1038/ncb3280

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Autonomy and non-autonomy of angiogenic cell movements revealed by experiment-driven mathematical modeling2015

    • Author(s)
      Sugihara K, Nishiyama K, Fukuhara S, Uemura A, Arima S, Kobayashi R, Kohn-Luque A, Mochizuki N, Suda T, Ogawa S, Kurihara H
    • Journal Title

      Cell Rep

      Volume: 13 Issue: 9 Pages: 1814-1827

    • DOI

      10.1016/j.celrep.2015.10.051

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Semaphorin-3C signals through Neuropilin-1 and PlexinD1 receptors to inhibit pathological angiogenesis.2015

    • Author(s)
      Yang WJ, Hu J, Uemura A, Tetzlaff F, Augustin HG, Fischer A.
    • Journal Title

      EMBO Mol Med.

      Volume: 7 Issue: 10 Pages: 1267-1284

    • DOI

      10.15252/emmm.201404922

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Therapeutic potential of semaphorin 3E for the treatment of choroidal neovascularization.2014

    • Author(s)
      Suda K, Guo C, Oishi A, Ikeda S, Uemura A, Yoshimura N
    • Journal Title

      Invest Ophthalmol Vis Sci

      Volume: 55 Issue: 8 Pages: 4700-4706

    • DOI

      10.1167/iovs.14-14087

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Vascular RhoJ is an effective and selective target for tumor angiogenesis and vascular disruption.2014

    • Author(s)
      Kim C, Yang H, Fukushima Y, Saw PE, Lee J, Park JS, Park I, Jung J, Kataoka H, Lee D, Heo WD, Kim I, Jon S, Adams RH, Nishikawa S, Uemura A, Koh GY
    • Journal Title

      Cancer Cell

      Volume: 25 Issue: 1 Pages: 102-117

    • DOI

      10.1016/j.ccr.2013.12.010

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Semaphorin-induced inflammation contributes to insulin resistance in dietary obesity.2013

    • Author(s)
      Shimizu I, Yoshida Y, Moriya J, Nojima A, Uemura A, Kobayashi Y, Minamino T.
    • Journal Title

      Cell Metab

      Volume: 18 Issue: 4 Pages: 491-504

    • DOI

      10.1016/j.cmet.2013.09.001

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] EphrinB2-EphB4 signals regulate formation and maintenance of funnel-shaped valves in corneal lymphatic capillaries.2013

    • Author(s)
      Katsuta H, Fukushima Y, Maruyama K, Hirashima M, Nishida K, Nishikawa S, Uemura A
    • Journal Title

      Invest Ophthalmol Vis Sci

      Volume: 54 Issue: 6 Pages: 4102-4108

    • DOI

      10.1167/iovs.12-11436

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of novel drug targets for the treatment of diabetic retinopathy.2013

    • Author(s)
      Uemura A
    • Journal Title

      Diabets Metab J

      Volume: 37 Issue: 4 Pages: 217-224

    • DOI

      10.4093/dmj.2013.37.4.217

    • Related Report
      2013 Annual Research Report
  • [Journal Article] 網膜血管新生における網羅遺伝子発現解析2013

    • Author(s)
      植村 明嘉
    • Journal Title

      血管医学

      Volume: 14 Pages: 369-375

    • Related Report
      2013 Annual Research Report
  • [Journal Article] 網膜症における血管新生2013

    • Author(s)
      植村 明嘉
    • Journal Title

      糖尿病合併症

      Volume: 27 Pages: 72-75

    • Related Report
      2013 Annual Research Report
  • [Presentation] ペリサイト消失による網膜血管バリア機能の破綻機構2015

    • Author(s)
      植村明嘉
    • Organizer
      第23回日本血管生物医学会シンポジウム
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2015-12-10
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 糖尿病網膜症に対する創薬開発2015

    • Author(s)
      植村明嘉
    • Organizer
      第54回日本網膜硝子体学会総会シンポジウム
    • Place of Presentation
      東京国際フォーラム(東京都千代田区)
    • Year and Date
      2015-12-04
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] ペリサイト消失による網膜血管バリア機能の破綻2015

    • Author(s)
      植村明嘉
    • Organizer
      第38回日本分子生物学会ワークショップ
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 糖尿病網膜症に対する創薬開発2015

    • Author(s)
      植村明嘉
    • Organizer
      第30回日本糖尿病合併症学会シンポジウム
    • Place of Presentation
      愛知県産業労働センターウインクあいち(名古屋市)
    • Year and Date
      2015-11-27
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 糖尿病網膜症モデルマウスを用いた創薬開発2015

    • Author(s)
      植村明嘉
    • Organizer
      第119回日本眼科学会総会シンポジウム
    • Place of Presentation
      ロイトン札幌
    • Year and Date
      2015-04-16
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Pathophysiology of pericy-free retinal vessels.2015

    • Author(s)
      Akiyoshi Uemura
    • Organizer
      Asia-ARVO 2015
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2015-02-16 – 2015-02-19
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Novel molecular targets for the treatment of diabetic retinopathy.2014

    • Author(s)
      Akiyoshi Uemura
    • Organizer
      2014 International Conference on Diabetes and Metabolism
    • Place of Presentation
      韓国イルサンKINTEX
    • Year and Date
      2014-10-16 – 2014-10-18
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] RhoJ defines angiogenic endothelial cell motility by integrating VEGF and Sema3E signals.2014

    • Author(s)
      Akiyoshi Uemura
    • Organizer
      18th International Vascular Biology Meeting
    • Place of Presentation
      京都市勧業館みやこめっせ
    • Year and Date
      2014-04-14 – 2014-04-17
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] RhoJ defines endothelial cell motility by integrating VEGF and Sema3E signals.2013

    • Author(s)
      Uemura A
    • Organizer
      EMBO Workshop. Semaphorin function and mechanism of action
    • Place of Presentation
      フランス
    • Related Report
      2013 Annual Research Report
  • [Presentation] RhoJ defines endothelial cell motility by integrating VEGF and Sema3E signals.2013

    • Author(s)
      Uemura A
    • Organizer
      Gordon Research Conference. Angiogenesis
    • Place of Presentation
      米国
    • Related Report
      2013 Annual Research Report
  • [Presentation] RhoJ integrates VEGF and Sema3E signals in angiogenic endothelial cells2013

    • Author(s)
      Uemura A
    • Organizer
      26th Spring Congress of the Korean Diabetes Association & 1st Korea-Japan Diabetes Forum
    • Place of Presentation
      韓国
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Regulation of ocular angiogenesis and lymphangiogenesis by guidance molecules.2013

    • Author(s)
      Uemura A
    • Organizer
      2nd Cornea Cell Biology Symposium at Wakayama
    • Place of Presentation
      和歌山
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 糖尿病網膜症に対する創薬標的分子の探索2013

    • Author(s)
      植村 明嘉
    • Organizer
      第67回日本臨床眼科学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 第21回日本血管生物医学会シンポジウム2013

    • Author(s)
      植村 明嘉
    • Organizer
      RhoJ defines endothelial cell motility by integrating VEGF and Sema3E signals
    • Place of Presentation
      大阪
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Patent(Industrial Property Rights)] METHOD FOR TARGETING VASCULAR RHOJ FOR INHIBITING TUMOR ANGIOGENESIS2014

    • Inventor(s)
      Akiyoshi Uemura et al.
    • Industrial Property Rights Holder
      KAIST
    • Industrial Property Rights Type
      特許
    • Filing Date
      2014-05-06
    • Related Report
      2014 Annual Research Report
    • Overseas

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Published: 2013-05-21   Modified: 2019-07-29  

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