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Elucidation of diversity and universality in angiogenesis by in vivo imaging

Research Project

Project/Area Number 16H05125
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General physiology
Research InstitutionNippon Medical School

Principal Investigator

Fukuhara Shigetomo  日本医科大学, 大学院医学研究科, 大学院教授 (70332880)

Research Collaborator Yuge Shinya  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywords血管新生 / 創傷治癒 / 虚血 / 内皮細胞 / ペリサイト / 蛍光イメージング / ゼブラフィッシュ / 血管内皮細胞 / イメージング / 腫瘍血管新生
Outline of Final Research Achievements

To investigate how endothelial cells (ECs) and pericytes (PCs) establish blood vessels during ischemia-induced angiogenesis, we developed a live-imaging system to analyze cutaneous angiogenesis in adult zebrafish. Cutaneous injury immediately induced angiogenesis. Tortuous and disorganized vessel networks formed within a few weeks after the injury and subsequently normalized through vessel regression in a few months. Upon injury, severed vessels elongated and anastomosed with each other. Thereafter, repaired vessels and adjacent uninjured vessels became tortuous by increasing the number of ECs. In parallel, PCs divided and migrated to cover the tortuous blood vessels. ECs sprouted from the PC-covered tortuous vessels, suggesting that EC sprouting does not require PC detachment from the vessel wall. Thus, live imaging of cutaneous angiogenesis in adult zebrafish enables us to clarify how ECs and PCs develop new blood vessels during cutaneous angiogenesis.

Academic Significance and Societal Importance of the Research Achievements

本研究では、創傷治癒に伴う血管新生において内皮細胞・ペリサイトが損傷部位に血管網を構築するプロセスの全貌を明らかにした。特に、血管新生におけるペリサイトの役割に関して、これまでの概念と矛盾する現象を捉え、血管新生におけるペリサイトの新たな役割を示した点で学術的な意義がある。また、癌や糖尿病網膜症では、病的な血管新生によってペリサイトの被覆が欠如した無秩序で機能的に未熟な血管が作られ病態を悪化させることから、病的血管新生が関わる疾患の病態解明、さらには治療法開発につながることが期待される。さらに、虚血性疾患などに対する効果的な血管再生療法の開発にも貢献できる。

Report

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

    (50 results)

All 2019 2018 2017 2016 Other

All Journal Article (11 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 10 results,  Open Access: 6 results,  Acknowledgement Compliant: 3 results) Presentation (36 results) (of which Int'l Joint Research: 6 results,  Invited: 26 results) Book (1 results) Remarks (2 results)

  • [Journal Article] Rap1b promotes Notch signal-mediated hematopoietic stem cell development by enhancing integrin-mediated cell adhesion.2019

    • Author(s)
      Rho S., Kobayashi I., Oguri-Nakamura E., Ando K., Fujiwara M., Kamimura N., Hirata H., Iida A., Iwai Y., Mochizuki N., Fukuhara S.
    • Journal Title

      Developmental Cell

      Volume: 印刷中 Issue: 5 Pages: 1-16

    • DOI

      10.1016/j.devcel.2019.03.023

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Live imaging of angiogenesis during cutaneous wound healing in adult zebrafish.2019

    • Author(s)
      Noishiki C., Yuge S., Ando K., Wakayama Y., Mochizuki N., Ogawa R., Fukuhara S.
    • Journal Title

      Angiogenesis

      Volume: 印刷中 Issue: 2 Pages: 341-354

    • DOI

      10.1007/s10456-018-09660-y

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Peri-arterial specification of vascular mural cells from na?ve mesenchyme requires Notch signaling2019

    • Author(s)
      Ando Koji、Wang Weili、Peng Di、Chiba Ayano、Lagendijk Anne K.、Barske Lindsey、Crump J. Gage、Stainier Didier Y. R.、Lendahl Urban、Koltowska Katarzyna、Hogan Benjamin M.、Fukuhara Shigetomo、Mochizuki Naoki、Betsholtz Christer
    • Journal Title

      Development

      Volume: 146 Pages: 165589-165589

    • DOI

      10.1242/dev.165589

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dynamic Regulation of Vascular Permeability by Vascular Endothelial Cadherin-Mediated Endothelial Cell-Cell Junctions2017

    • Author(s)
      Rho S., Ando K., Fukuhara S. (Corresponding author)
    • Journal Title

      Journal of Nippon Medical School

      Volume: 84 Issue: 4 Pages: 148-159

    • DOI

      10.1272/jnms.84.148

    • NAID

      130006140085

    • ISSN
      1345-4676, 1347-3409
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lysophosphatidic acid receptor 4 activation augments drug delivery in tumors by tightening endothelial cell-cell contact.2017

    • Author(s)
      Takara K., Eino D., Ando K., Yasuda D., Naito H., Tsukada Y., Iba T., Wakabayashi T., Muramatsu F., Kidoya H., Fukuhara S., Mochizuki N., Ishii S., Kishima H., Takakura N.
    • Journal Title

      Cell Reports

      Volume: 20 Issue: 9 Pages: 2072-2086

    • DOI

      10.1016/j.celrep.2017.07.080

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CCM2 and PAK4 act downstream of atrial natriuretic peptide signaling to promote cell spreading.2017

    • Author(s)
      Miura K, Nojiri T, Akitake Y, Ando K, Fukuhara S, Zenitani M, Kimura T, Hino J, Miyazato M, Hosoda H, Kangawa K.
    • Journal Title

      Biochem J.

      Volume: 474 Issue: 11 Pages: 1897-1918

    • DOI

      10.1042/bcj20160841

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 血管透過性のダイナミックかつ巧妙な制御を可能にするシグナル伝達系2017

    • Author(s)
      福原茂朋
    • Journal Title

      生化学

      Volume: 89 Pages: 368-376

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Flow-dependent endothelial YAP regulation that contributes to vessel maintenance.2017

    • Author(s)
      Nakajima H, Yamamoto K, Agarwala S, Terai K, Fukui H, Fukuhara S, Ando K, Miyazali T, Yokota Y, Sxhmelzer E, Belting H, Affolter M, Lecaudey, Mochizuki N
    • Journal Title

      Developmental Cell

      Volume: 40 Issue: 6 Pages: 523-536

    • DOI

      10.1016/j.devcel.2017.02.019

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Osteocrin, a secretory peptide from heart, contributes to cranial osteogenesis in zebrafish2016

    • Author(s)
      Chiba A, Watanabe-Takano H, Terai K, Fukui H, Miyazaki T, Uemura M, Hashimoto H, Hibi M, Fukuhara S, Mochizuki N
    • Journal Title

      Development

      Volume: 144 Pages: 334-344

    • DOI

      10.1242/dev.143354

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Clarification of mural cell coverage of vascular endothelial cells by live imaging of zebrafish.2016

    • Author(s)
      Ando K, Fukuhara S, Izumi N, Nakajima H, Fukui H, Kelsh RN, Mochizuki N.
    • Journal Title

      Development

      Volume: 143 Pages: 1328-1339

    • DOI

      10.1242/dev.132654

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Protein kinase A (PKA) Type I interacts with P-Rex1, a Rac guanine nucleotide exchange factor: Effect on PKA localization and P-Rex1 signaling.2016

    • Author(s)
      Chávez-Vargas L., Adame-García S.R., Cervantes-Villagrana R.D., Castillo-Kauil A., Bruystens J.G.H., Fukuhara S., Taylor S.S., Mochizuki N., Reyes-Cruz G., Vázquez-Prado J.
    • Journal Title

      J. Biol. Chem.

      Volume: 291 Issue: 12 Pages: 6182-6199

    • DOI

      10.1074/jbc.m115.712216

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Presentation] 創傷治癒に伴う血管新生のライブイメージングから明らかになった血管新生における内腔圧の新たな役割2019

    • Author(s)
      福原茂朋
    • Organizer
      日本薬学会 第139年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 血管新生におけるメカニカルストレスの新たな役割2019

    • Author(s)
      福原茂朋
    • Organizer
      第124回日本解剖学会総会・全国学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 血管形成の蛍光生体イメージング2018

    • Author(s)
      福原茂朋
    • Organizer
      第46回関東腎研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Angiogenesis and hematopoiesis: Lessons from zebrafish.2018

    • Author(s)
      Shigetomo Fukuhara
    • Organizer
      KAIST seminar
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 血管新生における内皮細胞移動メカニズム2018

    • Author(s)
      福原茂朋
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 蛍光生体イメージングにより明らかになった血管新生における内腔圧の新たな機能2018

    • Author(s)
      福原茂朋
    • Organizer
      第40回 生体膜と薬物の相互作用シンポジウム(日本薬学会)
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 創傷治癒における血管新生の蛍光ライブイメージング2018

    • Author(s)
      福原茂朋
    • Organizer
      生理学研究所 研究会2018「心臓・血管系の頑健性と精緻な制御を支える分子基盤の統合的解明」
    • Related Report
      2018 Annual Research Report
  • [Presentation] 蛍光イメージングが解き明かす血管構築メカニズム2018

    • Author(s)
      福原茂朋
    • Organizer
      第21 回血管病態研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Rap1b regulates hematopoietic stem cell development by promoting Notch signal-mediated specification of hemogenic endothelium2018

    • Author(s)
      Seung-Sik Rho, Isao Kobayashi, Koji Ando, Eri Oguri, Naoki Mochizuki, Shigetomo Fukuhara
    • Organizer
      International Vascular Biology Meeting 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Rap1b regulates hematopoietic stem cell development by promoting Notch signal-mediated specification of hemogenic endothelium2018

    • Author(s)
      Seung-Sik Rho, Isao Kobayashi, Koji Ando, Eri Oguri, Naoki Mochizuki, Shigetomo Fukuhara
    • Organizer
      SCB/EMBO 2018 Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 発生期腎臓において糸球体毛細血管が形成されるメカニズム2018

    • Author(s)
      西村裕介、一宮治美、渡部千里、依馬正次、望月直樹、福原茂朋
    • Organizer
      第26回日本血管生物医学会学術集会(心血管代謝週間〔CVMW〕2018)
    • Related Report
      2018 Annual Research Report
  • [Presentation] Rap1 GTPase regulates Notch-dependent hematopoietic stem cell development by promoting integrin-mediated cell adhesion2018

    • Author(s)
      Rho, S-S., Fukuhara, S
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] The small GTPase Rap1 regulates Notch signal-mediated hematopoietic stem cell development by enhancing integrin-mediated cell adhesion2018

    • Author(s)
      Rho, S-S., Fukuhara, S.
    • Organizer
      16th Korea-Japan Joint Symposium on Vascular Biology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 血管新生における内皮細胞の集団運動を制御す分子メカニズム2017

    • Author(s)
      福原茂朋、若山勇紀、藤原正和、園井理恵、望月直樹
    • Organizer
      第95回日本生理学会大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] これまでの血管研究を振り返って2017

    • Author(s)
      福原茂朋
    • Organizer
      第4回日本血管生物医学会若手研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 蛍光イメージングが解き明かす血管構築メカニズム2017

    • Author(s)
      福原茂朋
    • Organizer
      愛媛大学プロテオサイエンスセンターPROSセミナー
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Intravascular pressure restricts angiogenesis through mechanical stretching of endothelial cells2017

    • Author(s)
      Shigetomo Fukuhara
    • Organizer
      3rd International Symposium on Mechanobiology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 創傷治癒における血管新生のライブイメージングにより明らかになった新たな血管新生の制御機構2017

    • Author(s)
      福原茂朋
    • Organizer
      心血管代謝週間CVMW2017
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 創傷治癒過程の血管新生における内皮細胞・ペリサイト動態のライブイメージング2017

    • Author(s)
      福原茂朋
    • Organizer
      ConBio2017
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 蛍光生体イメージングによる血管新生研究2017

    • Author(s)
      福原茂朋
    • Organizer
      第5回細胞凝集研究会2017
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 蛍光イメージングが解き明かす血管構築メカニズム2017

    • Author(s)
      福原茂朋
    • Organizer
      関西血管生物研究会2017
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 血管形成と血管構造の安定化を司るシグナル伝達機構2017

    • Author(s)
      福原茂朋
    • Organizer
      第22回 近畿血栓症研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 蛍光生体イメージングによる血管構築メカニズム2017

    • Author(s)
      福原茂朋
    • Organizer
      第59回日本平滑筋学会総会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Live imaging of wound angiogenesis uncovers a novel inhibitory role of intravascular pressure in angiogenesis2017

    • Author(s)
      Shigetomo Fukuhara.
    • Organizer
      15th Japan-Korea Joint Symposium of Vascular Biology.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 蛍光生体イメージングにより明らかになった内腔圧による血管新生の新たな制御機構2017

    • Author(s)
      福原茂朋
    • Organizer
      Research Planet 2017
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 血管壁細胞のin vivoライブイメージング2016

    • Author(s)
      福原茂朋、安藤康史、望月直樹
    • Organizer
      第39回日本分子生物
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 血管新生の蛍光生体イメージング2016

    • Author(s)
      福原茂朋
    • Organizer
      慶応大学総合医科学研究センターセミナー
    • Place of Presentation
      慶応大学総合医科学研究棟7N6
    • Year and Date
      2016-11-17
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 血管新生の蛍光生体イメージング2016

    • Author(s)
      福原茂朋
    • Organizer
      東京大学代謝生理化学セミナー
    • Place of Presentation
      東京大学本郷キャンパス
    • Year and Date
      2016-10-27
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 創傷治癒に伴う血管新生のライブイメージングから明らかになった血管新生の新たな制御機構2016

    • Author(s)
      弓削進弥、國田樹、有馬勇一郎、横川隆司、三浦岳、望月直樹、西山功一、福原茂朋
    • Organizer
      生理学研究所研究会2016「心臓・血管系の包括的な機能統合研究」
    • Place of Presentation
      九州大学 馬出(病院地区)キャンパス
    • Year and Date
      2016-10-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] 血管新生における内皮細胞の一方向性移動を制御する分子機構2016

    • Author(s)
      福原茂朋、若山勇紀、望月直樹
    • Organizer
      第89回日本生化学会大会、シンポジウム「膜動態を介した細胞間・細胞外環境との相互作用の制御」
    • Place of Presentation
      東北大学川内北キャンパス
    • Year and Date
      2016-09-25
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 創傷治癒に伴う血管新生のライブイメージング2016

    • Author(s)
      福原茂朋
    • Organizer
      日本血管生物医学会秋期シンポジウム
    • Place of Presentation
      東京医科歯科大学
    • Year and Date
      2016-09-10
    • Related Report
      2016 Annual Research Report
  • [Presentation] 血管新生の蛍光生体イメージング2016

    • Author(s)
      福原茂朋
    • Organizer
      第84回日本医科大学医学会総会
    • Place of Presentation
      日本医科大学橘桜会館
    • Year and Date
      2016-09-03
    • Related Report
      2016 Annual Research Report
  • [Presentation] 血管形成と血管構造の安定化を司るシグナル伝達機構2016

    • Author(s)
      福原茂朋
    • Organizer
      第3回Nephrology Expert Conference (NEXT)
    • Place of Presentation
      アステラス製薬株式会社(東京)
    • Year and Date
      2016-07-20
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Live imaging of vascular development in zebrafish2016

    • Author(s)
      Shigetomo Fukuhara
    • Organizer
      New Era of Angiogenesis Research (Organized by Japan Vascular Biology and Medicine Organization)
    • Place of Presentation
      Grand Front Osaka
    • Year and Date
      2016-07-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] 血管新生の蛍光イメージング2016

    • Author(s)
      福原茂朋、望月直樹
    • Organizer
      第37回日本炎症・再生医学会、シンポジウム9「炎症と血管・リンパ管新生」
    • Place of Presentation
      京都市勧業館 みやこめっせ
    • Year and Date
      2016-06-17
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 血管新生におけるメカノトランスダクション機構の役割2016

    • Author(s)
      福原茂朋、望月直樹
    • Organizer
      第55回日本生体医工学会大会、オーガナイズドセッション「血管メカノバイオロジー研究の最前線」
    • Place of Presentation
      富山国際会議場
    • Year and Date
      2016-04-28
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Book] 医薬ジャーナル, 6月号特集「新しい医療を拓くメカノバイオロジー」 血管新生のメカノバイオロジー2017

    • Author(s)
      弓削進弥, 藤原正和, 福原茂朋
    • Publisher
      医薬ジャーナル
    • Related Report
      2017 Annual Research Report
  • [Remarks] http://www.nmsbyoutai.com

    • Related Report
      2018 Annual Research Report
  • [Remarks]

    • URL

      http://www.nmsbyoutai.com/

    • Related Report
      2016 Annual Research Report

URL: 

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

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