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Vessel maturation by a cytokine TGFbeta1 and crosstalk with VEGFR2 signaling

Research Project

Project/Area Number 25461132
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cardiovascular medicine
Research InstitutionKagawa University

Principal Investigator

Igarashi Junsuke  香川大学, 医学部, 准教授 (20346638)

Co-Investigator(Kenkyū-buntansha) HASHIMOTO TAKESHI  香川大学, 医学部, 助教 (80380153)
小坂 博昭  香川大学, 医学部, 教授 (60158897)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords血管新生 / 内皮細胞 / 受容体 / サイトカイン / 成長因子
Outline of Final Research Achievements

Angiogenesis is a process in which new blood vessels arise from pre-existing ones. A better understanding of angiogenesis may lead to a development of novel therapeutic interventions for a wide array of disease states.
In the present study, we focused on a maturation process of newly formed vessels, and revealed novel actions of a cytokine TGFbeta1. Furthermore, we have newly synthesized a pro-angiogenic adenosine-like agent termed COA-Cl. COA-Cl on the one hand induces VEGF to promote vessel sprouting from fibroblasts, and on the other hand stimulates S1P1 receptor in vascular endothelial cells to promote vessel maturation. Thus, these findings may contribute for the development of a pharmacological intervention to modulate angiogenic processes.

Report

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

    (16 results)

All 2016 2015 2014 2013

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (11 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results)

  • [Journal Article] Design, synthesis, and evaluation of novel 2-halogenated or aminated carbocyclic oxetanocin a analogs as potential angiogenic agents.2016

    • Author(s)
      Sakakibara N, Igarashi J, Takata M, Konishi R, Suzue N, Kato Y, Maruyama T, and Tsukamoto I.
    • Journal Title

      Heterocycles

      Volume: 印刷中

    • NAID

      40020609194

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A key role of PGC-1α transcriptional coactivator in production of VEGF by a novel angiogenic agent COA-Cl in cultured human fibroblasts.2016

    • Author(s)
      Igarashi J, Okamoto R, Yamashita T, Hashimoto T, Karita S, Nakai K, Kubota Y, Takata M, Yamaguchi F, Tokuda M, Sakakibara N, Tsukamoto I, Konishi R, Hirano K.
    • Journal Title

      Physiological Reports

      Volume: 4 Issue: 6 Pages: e12742-e12742

    • DOI

      10.14814/phy2.12742

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Synthesis and Evaluation of Novel Carbocyclic Oxetanocin A (COA-Cl) Derivatives as Potential Tube Formation Agents2015

    • Author(s)
      N. Sakakibara,* J. Igarashi, M. Takata, Y. Demizu, T. Misawa, M. Kurihara, R. Konishi, Y. Kato, T. Maruyama, I. Tsukamoto
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 63 Issue: 9 Pages: 701-709

    • DOI

      10.1248/cpb.c15-00386

    • NAID

      130005096030

    • ISSN
      0009-2363, 1347-5223
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Eicosapentaenoic acid upregulates VEGF-A through both GPR120 and PPARγ mediated pathways in 3T3-L1 adipocytes.2015

    • Author(s)
      Hasan AU, Ohmori K, Konishi K, Igarashi J, Hashimoto T, Kamitori K, Yamaguchi
    • Journal Title

      Mol Cell Endocrinol.

      Volume: 406 Pages: 10-18

    • DOI

      10.1016/j.mce.2015.02.012

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Involvement of S1P1 receptor pathway in angiogenic effects of a novel adenosine-like nucleic acid analog COA-Cl in cultured human vascular endothelial cells2014

    • Author(s)
      Igarashi J, Hashimoto T, Kubota Y, Shoji K, Maruyama T, Sakakibara N, TakuwaY, Ujihara Y, Katanosaka Y, Mohri S, Naruse K, Yamashita T, Okamoto R, Hirano K, Kosaka H, Takata M, Konishi R, Tsukamoto I.
    • Journal Title

      Pharmacology Research & Perspectives

      Volume: 2 Issue: 5 Pages: 68-68

    • DOI

      10.1002/prp2.68

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] COA-Cl(コアクロル)による血管新生促進作用に関わる細胞内情報伝達の仕組み2016

    • Author(s)
      五十嵐淳介
    • Organizer
      第93回日本生理学会大会
    • Place of Presentation
      北海道札幌市
    • Year and Date
      2016-03-22
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] A Key Role of PGC-1α Co-transcription Factor, but not HIF1α Transcription Factor, in Production of Vascular Endothelial Growth Factor (VEGF) by a Novel Angiogenic Agent COA-Cl in Cultured Human Fibroblasts.2015

    • Author(s)
      Okamoto R, Igarashi J, Yamashita T, Takeshi Hashimoto T, Karita S, Shoji K, Kubota Y, Takata M, Yamaguchi F, Tokuda M, Sakakibara N, Tsukamoto I, Konishi R, Hirano K.
    • Organizer
      Scientific Sessions 2015, American Heart Association
    • Place of Presentation
      アメリカ合衆国フロリダ州オーランド市
    • Year and Date
      2015-11-07
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Activation of cAMP/CREB/PGC-1α Pathway Plays a Key Role for a Novel Adenosine-like Angiogenic Agent COA-Cl to Induce Production of Vascular Endothelial Growth Gactor (VEGF) in Cultured Human Fibroblasts.2015

    • Author(s)
      Okamoto R, Igarashi J, Hashimoto T, Yamashita T, Shoji K, Kubota Y, Sakakibara N, Tsukamoto I, Konishi R, Hirano K.
    • Organizer
      Scientific Sessions 2015, American Heart Association
    • Place of Presentation
      アメリカ合衆国フロリダ州オーランド市
    • Year and Date
      2015-11-07
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 新規アデノシン類似化合物COA-Cl(コアクロル)はcAMP/CREB/PGC-1αの経路を介して血管内皮成長因子(VEGF)の産生を促進する2015

    • Author(s)
      岡本隆司、五十嵐淳介、橋本剛、山下哲生、苅田咲子、窪田泰夫、高田麻紀、小西良士、塚本郁子、平野勝也
    • Organizer
      第67回日本生理学会中国四国地方会
    • Place of Presentation
      鳥取県米子市
    • Year and Date
      2015-10-24
    • Related Report
      2015 Annual Research Report
  • [Presentation] 苅田咲子、五十嵐淳介、岡本隆司、山下哲生、橋本剛、窪田泰夫、塚本郁子、小西良士、平野勝也2015

    • Author(s)
      新規アデノシン類似化合物COA-Cl(コアクロル)はヒト皮膚由来線維芽細胞において結合組織成長因子(CTGF)の発現を抑制する
    • Organizer
      第67回日本生理学会中国四国地方会
    • Place of Presentation
      鳥取県米子市
    • Year and Date
      2015-10-24
    • Related Report
      2015 Annual Research Report
  • [Presentation] A novel adenosine-like angiogenic agent COA-Cl elevates VEGF production via the transcription co-activator PGC-1α in cultured human fibroblasts.2015

    • Author(s)
      Igarashi J, Tsukamoto I, Hirano K.
    • Organizer
      第79回日本循環器学会学術集会
    • Place of Presentation
      大阪府大阪市
    • Year and Date
      2015-04-24
    • Related Report
      2015 Annual Research Report
  • [Presentation] A novel angiogenic agent COA-Cl induced PGC-1α-mediated VEGF production in cultured human fibroblasts.2015

    • Author(s)
      Okamoto R, Igarashi J, Yamashita T, Hashimoto T, Shoji K, Kubota Y, Takata M, Tsukamoto I, Konishi R, Hirano K
    • Organizer
      第92回日本生理学会総会
    • Place of Presentation
      兵庫県神戸市
    • Year and Date
      2015-03-22 – 2015-03-24
    • Related Report
      2014 Research-status Report
  • [Presentation] 血管新生における内皮細胞の受容体シグナルの役割(教育講演)2014

    • Author(s)
      五十嵐淳介
    • Organizer
      第66回日本皮膚科学会西部支部学術大会
    • Place of Presentation
      香川県高松市
    • Year and Date
      2014-11-08 – 2014-11-09
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] アデノシン類似化合物COA-ClによるVEGF分泌促進機序の検討2014

    • Author(s)
      岡本隆司 五十嵐淳介 山下哲生 橋本剛 平野勝也 高田麻紀 小西良士 塚本郁子 小路和代 窪田泰夫
    • Organizer
      第66回日本生理学会中国四国地方会
    • Place of Presentation
      香川県高松市
    • Year and Date
      2014-11-01 – 2014-11-02
    • Related Report
      2014 Research-status Report
  • [Presentation] 新規核酸類似物質COA-Clによる血管新生反応におけるS1P1受容体の役割2014

    • Author(s)
      五十嵐淳介、窪田泰夫、小路和代、榊原紀和、丸山徳見、高田真紀、小坂博昭、多久和陽、橋本剛、山下哲生、小西良二、塚本郁子
    • Organizer
      第91回日本生理学会大会
    • Place of Presentation
      鹿児島市
    • Related Report
      2013 Research-status Report
  • [Presentation] S1P1 Receptors Mediate Angiogenic Responses Of A Novel Adenosine Analogue COA-Cl In Human Umbilical Vein Endothelial Cells (HUVEC)2013

    • Author(s)
      Junsuke Igarashi, Yasuo Kubota, Kazuyo Shoji, Norikazu Sakakibara, Tokumi Maruyama, Maki Takata, Hiroaki Kosaka, Ryoji Konishi, Ikuko Tsukamoto
    • Organizer
      Scientific Sessions, American Heart Association
    • Place of Presentation
      アメリカ合衆国テキサス州ダラス市
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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