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A Novel Strategy for Controlling Chronic Inflammation and Fibrosis: Targeting Sphingolipid Signaling

Research Project

Project/Area Number 26460374
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General medical chemistry
Research InstitutionIshikawa Prefectural Nursing University

Principal Investigator

Takuwa Noriko  石川県立看護大学, 看護学部, 教授 (70150290)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsスフィンゴシン-1-リン酸 / 情報伝達 / 慢性炎症 / 臓器線維化 / 脂質メディエーター / 細胞老化
Outline of Final Research Achievements

Molecular mechanism for organ fibrosis is not understood to date, with useful medicine to be developed. In our bloodstream is a lipid mediator named sphingosine-1-phosphate (S1P), which acts via 5 members of the S1P receptors to play diverse roles. S1P is also involved in pathophysiology of many kinds of diseases and disorders. We previously discovered that too much production of S1P in the heart in transgenic mice, which expressed high levels of S1P synthesizing enzyme, developed heart fibrosis spontaneously with age. In the present study we examined whether and how S1P signaling is involved in development of bleomycin (an anticancer chemotherapeutic that induce lung fibrosis as a side effect)-induced lung fibrosis. We found that one of the S1P receptors mediates aggravation of lung fibrosis, by using knockout mice and the S1P receptor subtype-specific antagonist, which is a promising candidate for treatment of human organ fibrosis.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (22 results)

All 2017 2016 2015 2014

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (20 results) (of which Int'l Joint Research: 3 results,  Invited: 7 results) Book (1 results)

  • [Journal Article] Phosphatidylinositol 3-kinase Class II α-Isoform PI3K-C2α Is Required for Transforming Growth Factor β-induced Smad Signaling in Endothelial Cells.2015

    • Author(s)
      Aki S, Yoshioka K, Okamoto Y, Takuwa N, Takuwa Y.
    • Journal Title

      J Biol Chem.

      Volume: 290 Issue: 10 Pages: 6086-6105

    • DOI

      10.1074/jbc.m114.601484

    • NAID

      120005593954

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Phosphoinositide-specific 3'-phosphatase, myotubularin-related protein 4 (MTMR4), regulates lysosomal activity and autophagy.2017

    • Author(s)
      Pham Quynh Hoa, Kazuaki Yoshioka, Sato Nakamura, MD Azadul Kabir Sarker, Khin Thuzar Aung, Shahidul Islam, Sho Aki, Noriko Takuwa and Yoh Takuwa.
    • Organizer
      第94回日本生理学会大会
    • Place of Presentation
      浜松
    • Year and Date
      2017-03-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] Phosphotidylinositol 3-kinase class II isoforms, PI3K-C2alpha and PI3K-C2beta are necessary for pinocytosis in endothelial cells.2017

    • Author(s)
      Khin Thuzar Aung, Sho Aki, Kazuaki Yoshioka, Pham Hoa Quynh , MD Azadul Kabir Sarker, Islam Shahidul, Noriko Takuwa, Yoh Takuwa.
    • Organizer
      第94回日本生理学会大会
    • Place of Presentation
      浜松
    • Year and Date
      2017-03-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] Endothelial  Class II PI3K-C2alpha is Necessary for Vasucular Formation and Integrity through Regulating Endocytic Membrane Trafficking.2017

    • Author(s)
      Kazuaki Yoshioka, Sho Aki, Noriko Takuwa, Yoh Takuwa.
    • Organizer
      第81回日本循環器学会学術集会
    • Place of Presentation
      金沢
    • Year and Date
      2017-03-18
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Phosphatidylinositol 3-kinase class IIalpha isoform PI3K-C 2alpha is required for transforming growth factor β-induced receptor endocytosis and endosomal signaling in endothelial cells.2016

    • Author(s)
      Sho Aki, Kazuaki Yoshioka, Yasuo Okamoto, Noriko Takuwa , Pham Quynh Hoa, MD Azadul Kabir Sarker, Khin Thuzar Aung, Shahidul Islam, Yoh Takuwa.
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] S1P2, a receptor for the lysophospholipid mediator sphingosine 1-phosphate,2016

    • Author(s)
      Yasuo Okamoto, Hong Cui, Kazuaki Yoshioka, Noriko Takuwa, Toshishige Shibamoto, Yoh Takuwa.
    • Organizer
      International Shock Congress Symposium "Microcirculation and endothelial damage in sepsis and shock"
    • Place of Presentation
      東京
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 宿主細胞のスフィンゴシン-1-リン酸受容体を介する がん血行性転移の制御2016

    • Author(s)
      多久和典子, 岡本安雄, 多久和 陽
    • Organizer
      第26回日本病態生理学会大会
    • Place of Presentation
      石川
    • Year and Date
      2016-08-05
    • Related Report
      2016 Annual Research Report
  • [Presentation] S1P2 による血管新生と血管障壁機能の制御 (シンポジウム 招待講演)2016

    • Author(s)
      岡本安雄、杜娃、崔弘、吉岡和晃、多久和典子、多久和陽.
    • Organizer
      第58回 日本脂質生化学会
    • Place of Presentation
      秋田
    • Year and Date
      2016-06-09
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Phosphatidylinositol 3-kinase class IIαisoform PI3K-C2alpha is required for transforming growth factor β-induced receptor endocytosis and endosomal signaling in endothelial cells.2016

    • Author(s)
      Sho Aki, Kazuaki Yoshioka, Yasuo Okamoto, Noriko Takuwa and Yoh Takuwa
    • Organizer
      The 2nd Spring Special Symposium of the Japanese Vascular Biology and Medicine Organization
    • Place of Presentation
      大阪
    • Year and Date
      2016-06-03
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 血管内皮細胞においてクラスII 型PI3K-C2α はTGFβ/Smad シグナル伝達系に必須である2016

    • Author(s)
      安藝翔、吉岡和晃、岡本安雄、多久和典子、多久和陽
    • Organizer
      第93回日本生理学会
    • Place of Presentation
      札幌コンベンションセンター(札幌市)
    • Year and Date
      2016-03-22
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Deletion of sphingosine 1-phospahte (S1P) receptor-2 (S1P-2-) inhibits lung fibrosis through altering alveolar macrophage polarization and senescence in mice.2015

    • Author(s)
      Juan juan Zhao Yasuo Okamoto Kazuaki Yoshioka Sho Aki Pham Quynh Hoa Azadul MD Kabir Sarker Khin Thuzar Aung Noriko Takuwa Yutaka Inagaki Chiaki Takahashi Takashi Wada Yoh Takuwa
    • Organizer
      第38回日本分子生物学会・第88回日本生化学会
    • Place of Presentation
      神戸ポートアイランド(神戸ポートピアホテル 神戸国際会議場 神戸国際展示場 神戸商工会議所)(兵庫県神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] クラス II PI3-キナーゼ PI3K-C2αはエンドソーム上でのTGFβ/Smad2/3シグナリングに必須である2015

    • Author(s)
      安藝 翔、吉岡 和晃、岡本 安雄、多久和 典子、多久和 陽
    • Organizer
      第62回 中部日本生理学会
    • Place of Presentation
      富山大学 五福キャンパス 黒田講堂(富山県富山市)
    • Year and Date
      2015-11-13
    • Related Report
      2015 Research-status Report
  • [Presentation] Role of S1P2 in inflammation and fibrosis.2015

    • Author(s)
      Yoh Takuwa Juanjuan Zhao, Yasuo, Okamoto, Kazuaki Yoshioka and Noriko Takuwa.
    • Organizer
      14 th International Conference on Bioactive Lipids in Cancer, Inflammation, and Related Diseases
    • Place of Presentation
      Sofitel Chain Bridge Hotel(ハンガリー ブタペスト)
    • Year and Date
      2015-07-12
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Phosphatidylinositol 3-kinase class II a isoform PI3K-C2a is required for transforming growth factor b-induced receptor endocytosis and endosomal signaling in endothelial cells.2015

    • Author(s)
      Sho Aki, Kazuaki Yoshioka, Yasuo, Okamoto, Noriko Takuwa and Yoh Takuwa.
    • Organizer
      14 th International Conference on Bioactive Lipids in Cancer, Inflammation, and Related Diseases
    • Place of Presentation
      Sofitel Chain Bridge Hotel(ハンガリー ブタペスト)
    • Year and Date
      2015-07-12
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Sphingosine 1-phosphate receptor-2 plays a protective role against anaphylaxis and acute lung injury2015

    • Author(s)
      Yasuo Okamoto, Hong Cui, Kazuaki Yoshioka, Noriko Takuwa, Yoh Takuwa
    • Organizer
      第10回スフィンゴテラピィ(STC)研究会
    • Place of Presentation
      ホテルアローレ(石川県)
    • Year and Date
      2015-06-16
    • Related Report
      2015 Research-status Report
  • [Presentation] クラスII α型PI3K-C2αはエンドソーム上でのTGFβ/Smad2/3 シグナリングに必須である2015

    • Author(s)
      安藝 翔、吉岡 和晃、岡本 安雄、多久和 典子、多久和 陽
    • Organizer
      第57回 日本脂質生化学会
    • Place of Presentation
      一橋大学一橋講堂(東京)
    • Year and Date
      2015-05-28
    • Related Report
      2015 Research-status Report
  • [Presentation] Sphingosine 1-phosphate receptor-2 plays a protective role against lipopolysaccharide (LPS)-induced acute lung injury.2015

    • Author(s)
      Yasuo Okamoto, Hong Cui, Kazuaki Yoshioka, Noriko Takuwa, Sho Aki, JuanJuan Zhao, Hoa Quynh Pham, Md. Azadul Kabir Sarker, Saori Koizumi, Yoh Takuwa
    • Organizer
      第92回日本生理学会
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2015-03-21 – 2015-03-23
    • Related Report
      2014 Research-status Report
  • [Presentation] 292.安藝翔、吉岡和晃、多久和 典子、岡本安雄、多久和陽 クラスII 型PI3 キナーゼ-C2α によるTGFβ 血管内皮作用の調節機構2014

    • Author(s)
      安藝翔、吉岡和晃、多久和 典子、岡本安雄、多久和陽
    • Organizer
      第61回中部日本生理学会
    • Place of Presentation
      名古屋市立大学桜山キャンパス(愛知県名古屋市)
    • Year and Date
      2014-11-06 – 2014-11-07
    • Related Report
      2014 Research-status Report
  • [Presentation] クラスIIα型PI3K-C2αはALK5 内在化及び足場タンパクSARA のエンドソームへの動員を制御しTGFβ1-Smad2/3 を介した血管新生を調節する2014

    • Author(s)
      安藝 翔、吉岡 和晃、岡本 安雄、多久和 典子、多久和 陽
    • Organizer
      第56回 日本脂質生化学会
    • Place of Presentation
      近畿大学東大阪キャンパス(大阪府東大阪市)
    • Year and Date
      2014-06-06 – 2014-06-07
    • Related Report
      2014 Research-status Report
  • [Presentation] Sphingosine-1-phosphate receptor-2 (S1P2) negatively regulates eNOS and protects against acute vascular barrier disruption.2014

    • Author(s)
      Yasuo Okamoto, Cui Hong, Kazuaki Yoshioka, Noriko Takuwa, Toshishige Shibamoto, Yoh Takuwa
    • Organizer
      The 18th International Vascular Biology Meeting 2014 (IVBM 2014)
    • Place of Presentation
      みやこめっせ(京都府京都市)
    • Year and Date
      2014-04-14 – 2014-04-17
    • Related Report
      2014 Research-status Report
  • [Presentation] Distinct role of S1P2 in the functional regulation of vascular endothelium and smooth muscle.2014

    • Author(s)
      Yoh Takuwa, Yasuo Okamoto, Kazuaki Yoshioka, Noriko Takuwa
    • Organizer
      The 18th International Vascular Biology Meeting 2014 (IVBM 2014)
    • Place of Presentation
      みやこめっせ(京都府京都市)
    • Year and Date
      2014-04-14 – 2014-04-17
    • Related Report
      2014 Research-status Report
    • Invited
  • [Book] Bioactive Lipid Mediators2017

    • Author(s)
      Takuwa N, OkamotoY, Yoshioka K and Takuwa Y.
    • Publisher
      Springer Japan
    • Related Report
      2015 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2025-11-19  

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