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Vascular stabilization and destabilization by angiopoietin-1/Tie2 system

Research Project

Project/Area Number 22390040
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General physiology
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

FUKUHARA Shigetomo  独立行政法人国立循環器病研究センター, 研究所, 室長 (70332880)

Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥14,820,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥3,420,000)
Fiscal Year 2012: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2011: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2010: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Keywordsアンジオポエチン / Tie2 / 血管新生 / 血管安定化 / Tie-2 / アンンジオポエチン
Research Abstract

In this study, we investigated the mechanism how Angiopoietin-1 (Ang1)-Tie2 signal promotes vascular stabilization. Here, we show that Ang1-Tie2 signal potentiates Notch signal through β-catenin-dependent up-regulation of Delta-like 4 expression, leading to basement membrane formation required for vascular stabilization. In addition, we report that Ang1-Tie2 signal induces reorganization of actin cytoskeleton through Rap1 small GTPase, thereby enhancing endothelial barrier function.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (58 results)

All 2013 2012 2011 2010 Other

All Journal Article (14 results) (of which Peer Reviewed: 14 results) Presentation (20 results) Book (19 results) Remarks (5 results)

  • [Journal Article] PDZ-RhoGEF and LARG are essential for embryo development, and provide a link between thrombin and LPA receptors and Rho activation.2013

    • Author(s)
      Mikelis et al.
    • Journal Title

      J. Biol. Chem.

      Volume: 288 Issue: 17 Pages: 12232-12243

    • DOI

      10.1074/jbc.m112.428599

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The sphingosine-1-phosphate transporter Spns2 expressed on endothelial cells regulates lymphocyte trafficking in mice2012

    • Author(s)
      Fukuhara S, et al
    • Journal Title

      J Clin Invest

      Volume: (In press)(未定) Issue: 4 Pages: 1416-1426

    • DOI

      10.1172/jci60746

    • Related Report
      2012 Annual Research Report 2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Arhgef15 promotes retinal angiogenesis by mediating VEGF-induced Cdc42 activation and potentiating RhoJ inactivation in endothelial cells.2012

    • Author(s)
      Kusuhara S., Fukushima Y., Fukuhara S., Jakt L.M., Okada M., Shimizu Y., Hata M., Nishida K., Negi A., Hirashima M., Mochizuki N., Nishikawa S. and Uemura A.
    • Journal Title

      PLoS One

      Volume: 7 Issue: 9 Pages: e45858-e45858

    • DOI

      10.1371/journal.pone.0045858

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cardiac connexins, mutations and arrhythmias2012

    • Author(s)
      Delmar M, Makita N
    • Journal Title

      Curr Opin Cardiol

      Volume: (in press) Issue: 1 Pages: 163-172

    • DOI

      10.1161/circep.111.967604

    • Related Report
      2012 Annual Research Report 2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cytochalasin D enhances the accumulation of a protease-resistant form of prion protein in ScN2a Cells: Involvement of PI3 kinase/Akt signaling pathway.2012

    • Author(s)
      Takenouchi T. et al.
    • Journal Title

      Cell Biol. Int.

      Volume: 36 Issue: 12 Pages: 1223-1231

    • DOI

      10.1042/cbi20120329

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tumor cell-derived angiopoietin-like protein ANGPTL2 is a critical driver of metastasis2012

    • Author(s)
      Endo M, et al
    • Journal Title

      Cancer Research

      Volume: 72 Issue: 7 Pages: 1784

    • DOI

      10.1158/0008-5472.can-11-3878

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] EphrinA/EphA signal facilitates insulin-like growth factor-I-induced myogenic differentiation through suppression of the Ras/extracellular signal-regulated kinase 1/2 cascade in myoblast cell lines2011

    • Author(s)
      Minami M., et al
    • Journal Title

      Molecular Biology of the Cell

      Volume: 22 Issue: 18 Pages: 3508-3519

    • DOI

      10.1091/mbc.e11-03-0183

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Angiopoietin-1/Tie2 signal augments basal Notch signal controlling Vascular quiescence by inducing delta-like 4 expression through AKT-mediated activation of β-catenin2011

    • Author(s)
      Zhang J., et al
    • Journal Title

      Journal of Biological Chemistry

      Volume: 286 Issue: 10 Pages: 8055-8066

    • DOI

      10.1074/jbc.m110.192641

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Angiopoietin-1/Tie2 signal augments basal Notch signal controlling vascular quiescence by inducing delta-like 4 expression through AKT-mediated activation of・-catenin.2011

    • Author(s)
      Zhang J.
    • Journal Title

      J.Biol.Chem.

      Volume: 286 Pages: 8055-8066

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Vascular endothelial-cadherin stabilizes at cell-cell junctions by anchoring to circumferential actin bundles through α- and β-catenins in cyclic AMP-Epac-Rap1 signal-activated endothelial cells.2010

    • Author(s)
      Noda K., Zhang J., Fukuhara S., Kunimoto S., Yoshimura M. and Mochizuki N.
    • Journal Title

      Mol. Biol. Cell

      Volume: 21 Issue: 4 Pages: 584-596

    • DOI

      10.1091/mbc.e09-07-0580

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Angiopoietin-1/Tie2 receptor signaling in vascular quiescence and angiogenesis.2010

    • Author(s)
      Fukuhara S., Sako K., Noda K., Zhang J., Minami M. and Mochizuki N.
    • Journal Title

      Histol. Histopathol.

      Volume: 25 Pages: 384-396

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/20054809

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Vascular endothelial-cadherin stabilizes at cell-cell junctions by anchoring to circumferential actin bundles through・- and・-catenins in cyclic AMP-Epac-Rap1 signal-activated endothelial cells.2010

    • Author(s)
      Noda K.
    • Journal Title

      Mol.Biol.Cell

      Volume: 21 Pages: 584-596

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Angiopoietin-1/Tie2 receptor signaling in vascular quiescence and angiogenesis.2010

    • Author(s)
      Fukuhara S.
    • Journal Title

      Histol.Histopathol.

      Volume: 25 Pages: 387-396

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Establishment of mice expressing EGFP in the placode-derived inner ear sensory cell lineage and FACS-array analysis focused on the regional specificity of the otocyst.2010

    • Author(s)
      Fujimoto C.
    • Journal Title

      J.Comp.Neurol.

      Volume: 518 Pages: 4702-4722

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] スフィンゴシン-1-リン酸を介した血管内皮細胞による免疫系の制御2013

    • Author(s)
      福原茂朋
    • Organizer
      第42回日本心脈管作動物質学会、シンポジウム2「心血管病研究の最前線」
    • Place of Presentation
      奈良
    • Year and Date
      2013-02-09
    • Related Report
      2012 Final Research Report
  • [Presentation] スフィンゴシン-1-リン酸を介した血管内皮細胞による免疫系の制御2013

    • Author(s)
      福原茂朋
    • Organizer
      第42回日本心脈管作動物質学会
    • Place of Presentation
      奈良
    • Related Report
      2012 Annual Research Report
  • [Presentation] In vivo imaging of signal transduction pathways involved in angiogenesis2012

    • Author(s)
      Shigetomo Fukuhara, Naoki Mochizuki
    • Organizer
      The 10th Korea-Japan Joint Symposium on Vascular Biology & The 20th Annual Meeting of the Japanese Vascular Biology and Medicine Organization. Symposium.
    • Place of Presentation
      Tokushima, Japan
    • Year and Date
      2012-12-05
    • Related Report
      2012 Final Research Report
  • [Presentation] スフィンゴシン-1-リン酸トランスポーターSpns2の生理的機能2012

    • Author(s)
      福原茂朋
    • Organizer
      生理研研究会「細胞センサーの分子機構・相互関連・ネットワーク研究会」
    • Place of Presentation
      岡崎
    • Year and Date
      2012-11-30
    • Related Report
      2012 Final Research Report
  • [Presentation] イメージングによる血管新生メカニズムの解析2012

    • Author(s)
      福原茂朋
    • Organizer
      日本動物学会第83回大会、シンポジウム「神経系・血管系の新生と再生に関する最近の進展と展望」
    • Place of Presentation
      大阪
    • Year and Date
      2012-09-13
    • Related Report
      2012 Final Research Report
  • [Presentation] 蛍光生体イメージングによる血管新生メカニズムの解析2012

    • Author(s)
      福原茂朋
    • Organizer
      第22回日本数理生物学会、シンポジウム
    • Place of Presentation
      岡山
    • Year and Date
      2012-09-12
    • Related Report
      2012 Final Research Report
  • [Presentation] In vivo imaging of signal transduction pathways involved in angiogenesis2012

    • Author(s)
      Shigetomo Fukuhara
    • Organizer
      第42回日本心脈管作動物質学会
    • Place of Presentation
      徳島
    • Related Report
      2012 Annual Research Report
  • [Presentation] スフィンゴシン-1-リン酸トランスポーターSpns2の生理的機能2012

    • Author(s)
      福原茂朋
    • Organizer
      生理研研究会「細胞センサーの分子機構・相互関連・ネットワーク研究会」
    • Place of Presentation
      岡崎
    • Related Report
      2012 Annual Research Report
  • [Presentation] イメージングによる血管新生メカニズムの解析2012

    • Author(s)
      福原茂朋
    • Organizer
      日本動物学会第83回大会
    • Place of Presentation
      大阪
    • Related Report
      2012 Annual Research Report
  • [Presentation] 蛍光生体イメージングによる血管新生メカニズムの解析2012

    • Author(s)
      福原茂朋
    • Organizer
      第22回日本数理生物学会
    • Place of Presentation
      岡山
    • Related Report
      2012 Annual Research Report
  • [Presentation] Visualization of endothelial cell cycle progression during vascular network formation2011

    • Author(s)
      福原茂朋
    • Organizer
      第19回日本血管生物医学会
    • Place of Presentation
      東京・東京ステーションコンファレンス
    • Year and Date
      2011-12-09
    • Related Report
      2011 Annual Research Report
  • [Presentation] Visualization of endothelial cell dynamics during vascular network formation by in vivo bioimaging2011

    • Author(s)
      Shigetomo Fukuhara
    • Organizer
      Cell Signaling Network 2011. Symposium
    • Place of Presentation
      Merida, Mexico
    • Year and Date
      2011-10-26
    • Related Report
      2012 Final Research Report
  • [Presentation] Visualization of endothelial cell cycle progression during vascular network formation2011

    • Author(s)
      Shigetomo Fukuhara
    • Organizer
      The Satellite Meeting in Osaka for the 2^<nd> Pacific Symposium on Vascular Biology
    • Place of Presentation
      大阪・大阪大学
    • Year and Date
      2011-10-26
    • Related Report
      2011 Annual Research Report
  • [Presentation] Visualization of endothelial cell dynamics during vascular network formation by in vivo bioimaging2011

    • Author(s)
      Shigetomo Fukuhara
    • Organizer
      Cell Signaling Network 2011
    • Place of Presentation
      Yucatan, Merida, Mexico
    • Year and Date
      2011-10-26
    • Related Report
      2011 Annual Research Report
  • [Presentation] 生体蛍光イメージングによる血管ネットワーク形成機構の解析2011

    • Author(s)
      福原茂朋、望月直樹
    • Organizer
      第84回日本生化学、シンポジウム
    • Place of Presentation
      京都
    • Year and Date
      2011-09-24
    • Related Report
      2012 Final Research Report
  • [Presentation] 生体蛍光イメージングによる血管ネットワーク形成機構の解析2011

    • Author(s)
      福原茂朋
    • Organizer
      第84回日本生化学
    • Place of Presentation
      京都・国立京都国際会館
    • Year and Date
      2011-09-24
    • Related Report
      2011 Annual Research Report
  • [Presentation] 蛍光イメージングを用いたin vivo細胞生物学による血管形成機構の解析2011

    • Author(s)
      福原茂朋
    • Organizer
      第63回日本細胞生物学会
    • Place of Presentation
      札幌・北海道大学
    • Year and Date
      2011-06-27
    • Related Report
      2011 Annual Research Report
  • [Presentation] Signaling pathways regulating endothelial barrier functions2010

    • Author(s)
      Shigetomo Fukuhara, Koji Ando, Kazuomi Noda, Jianghui Zhang, Naoki Mochizuki
    • Organizer
      The 8th Korea-Japan Joint Symposium on Vascular Biology & The 18th Annual Meeting of the Japanese Vascular Biology and Medicine Organization. Symposium.
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      2010-12-03
    • Related Report
      2012 Final Research Report
  • [Presentation] Signaling pathways regulating endothelial barrier functions2010

    • Author(s)
      Fukuhara S.
    • Organizer
      The 8th Korea-Japan Joint Symposium on Vascular Biology & The 18th Annual Meeting of the Japanese Vascular Biology and Medicine Organization. (Symposium)
    • Place of Presentation
      大阪
    • Year and Date
      2010-12-03
    • Related Report
      2010 Annual Research Report
  • [Presentation] Visualization of endothelial cell cycle progression in vivo2010

    • Author(s)
      Fukuhara S.
    • Organizer
      武田国際シンポジウム「Casting Light on Life」
    • Place of Presentation
      東京
    • Year and Date
      2010-12-01
    • Related Report
      2010 Annual Research Report
  • [Book] 「血管新生に関わる細胞内シグナル伝達」、血管新生研究の最先端2013

    • Author(s)
      福原 茂朋
    • Publisher
      医薬ジャーナル社
    • Related Report
      2012 Final Research Report
  • [Book] 血管新生研究の最先端、「in vivoイメージング」2013

    • Author(s)
      若山 勇紀、福原 茂朋
    • Total Pages
      10
    • Publisher
      医薬ジャーナル社
    • Related Report
      2012 Annual Research Report
  • [Book] Signaling pathways regulating endothelial cell-cell junctions as a barrier to tumor metastasis. In “Tight junctions in cancer metastasis”2013

    • Author(s)
      Fukuhara S. et al.
    • Total Pages
      15
    • Publisher
      Springer
    • Related Report
      2012 Annual Research Report
  • [Book]2012

    • Publisher
      メディカルビュー社
    • Related Report
      2012 Final Research Report
  • [Book] 「蛍光生物学」の最前線8-1「ゼブラフィッシュの蛍光イメージングによる血管形成メカニズムの解析」2012

    • Author(s)
      福原 茂朋、若山 勇紀
    • Publisher
      DOJIN News
    • Related Report
      2012 Final Research Report
  • [Book] 血管新生研究の最先端、「血管新生に関わる細胞内シグナル伝達」2012

    • Author(s)
      福原 茂朋
    • Total Pages
      8
    • Publisher
      医薬ジャーナル社
    • Related Report
      2012 Annual Research Report
  • [Book] 再生医療、学会印象記「第19回日本血管生物医学会学術集会」2012

    • Author(s)
      福原 茂朋
    • Total Pages
      2
    • Publisher
      メディカルビュー社
    • Related Report
      2012 Annual Research Report
  • [Book] 「細胞小器官と細胞骨格」「PECAM-1」「カドヘリン」、血管生物学辞典2011

    • Author(s)
      福原 茂朋
    • Publisher
      朝倉書店
    • Related Report
      2012 Final Research Report
  • [Book] 血管医学,生きた細胞・生物を用いた血管構築を理解するためのイメージング2011

    • Author(s)
      福原茂朋
    • Total Pages
      8
    • Publisher
      メディカルビュー社
    • Related Report
      2011 Annual Research Report
  • [Book] 血管内皮細胞間接着を制御するシグナル伝達機構、薬学雑誌2010

    • Author(s)
      福原 茂朋、望月 直樹
    • Publisher
      日本薬学会
    • Related Report
      2012 Final Research Report
  • [Book] アンジオポエチン-1 による血管安定化メカニズム、日本薬理学雑誌くすりとからだ2010

    • Author(s)
      福原 茂朋、望月 直樹
    • Publisher
      日本薬理学会
    • Related Report
      2012 Final Research Report
  • [Book] 血管内皮細胞間接着による血管安定化・成熟化、実験医学(増刊 : 血管研究と血管治療)2010

    • Author(s)
      福原 茂朋、張 江暉、野田 一臣、望月 直樹
    • Publisher
      羊土社
    • Related Report
      2012 Final Research Report
  • [Book] 血管新生・恒常性の維持、生化学2010

    • Author(s)
      福原 茂朋、望月 直樹
    • Publisher
      日本生化学会
    • Related Report
      2012 Final Research Report
  • [Book] Ang1-Tie2による血管透過性制御、Annual Review循環器2010

    • Author(s)
      福原 茂朋、望月 直樹
    • Publisher
      中外医学社
    • Related Report
      2012 Final Research Report
  • [Book] Annunal Review循環器2010(Ang1-Tie2による血管透過性制御)2010

    • Author(s)
      福原茂朋
    • Total Pages
      7
    • Publisher
      中外医学社
    • Related Report
      2010 Annual Research Report
  • [Book] 血管内皮細胞間接着を制御するシグナル伝達機構2010

    • Author(s)
      福原茂朋
    • Total Pages
      8
    • Publisher
      薬学雑誌
    • Related Report
      2010 Annual Research Report
  • [Book] 血管内皮細胞間接着による血管安定化・成熟化、実験医学(増刊:血管研究と血管治療)2010

    • Author(s)
      福原茂朋
    • Total Pages
      7
    • Publisher
      羊土社
    • Related Report
      2010 Annual Research Report
  • [Book] アンジオポエチン-1による血管安定化メカニズム2010

    • Author(s)
      福原茂朋
    • Total Pages
      5
    • Publisher
      日本薬理学雑誌くすりとからだ
    • Related Report
      2010 Annual Research Report
  • [Book] 血管新生・恒常性の維持2010

    • Author(s)
      福原茂朋
    • Total Pages
      12
    • Publisher
      生化学
    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.ncvc.go.jp/res/divisions/structural_analysis/index.html

    • Related Report
      2012 Final Research Report
  • [Remarks]

    • URL

      http://plaza.umin.ac.jp/~ncvc/

    • Related Report
      2012 Final Research Report
  • [Remarks]

    • URL

      http://www.ncvc.go.jp/res/divisions/structural_analysis/index.html

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://plaza.umin.ac.jp/ncvc/index.html

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.ncvc.go.jp/res/divisions/structural_analysis/index.html

    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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