A novel strategy of acute lung injury: Targeting sphingolipid signaling

• Project/Area Number: 15K10970
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Kawasaki Medical School (2016-2017); Kanazawa University (2015)
• Principal Investigator: Okamoto Yasuo 川崎医科大学, 医学部, 教授 (80293877)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: スフィンゴシン1-リン酸 / 急性肺損傷 / 血管バリア機能 / リポポリサッカライド

Outline of Final Research Achievements

Sphingosine　1-phosphate (S1P) is a lysophospholipid mediator and plays an important role in the regulation of vascular barrier function. In this study, we found that S1P2 mediates the protection from acute lung injury possibly through inhibiting endothelial nitric oxide synthase, pointing to S1P2 as a promising novel target for treating acute lung injury.

Research Products

• [Journal Article] Sphingosine-1-phosphate receptor-2 facilitates pulmonary fibrosis through potentiating IL-13 pathway in macrophages. (2018)
  • Author(s): 1.Zhao J, Okamoto Y, Asano Y, Ishimaru K, Aki S, Yoshioka K, Takuwa N, Wada T, Inagaki Y, Takahashi C, Nishiuchi T, Takuwa Y
  • Journal Title: PLoS One Volume: 印刷中
  • NAID: 120006605152
  • Peer Reviewed / Open Access
• [Journal Article] Augmented sphingosine 1 phosphate receptor-1 signaling in cardiac fibroblasts induces cardiac hypertrophy and fibrosis through angiotensin II and interleukin-6. (2017)
  • Author(s): Ohkura SI, Usui S, Takashima SI, Takuwa N, Yoshioka K, Okamoto Y, Inagaki Y, Sugimoto N, Kitano T, Takamura M, Wada T, Kaneko S, Takuwa Y.
  • Journal Title: PLoS One. Volume: 12 Issue: 8 Pages: e0182329-e0182329
  • DOI: 10.1371/journal.pone.0182329
  • Peer Reviewed / Open Access
• [Journal Article] Sphingosine-1-phosphate receptor type 2 (S1P2) inhibits bleomycininduced cellular senescence in murine lung fibroblasts (2016)
  • Author(s): Juanjuan Zhao, Yasuo Okamoto, Yoh Takuwa
  • Journal Title: 十全医学会雑誌 Volume: 125
  • Peer Reviewed / Acknowledgement Compliant
• [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
  • Peer Reviewed / Open Access
• [Journal Article] 脂質メディエータースフィンゴシン1-リン酸による血管障壁機能の制御 (2015)
  • Author(s): 岡本安雄
  • Journal Title: 十全医学会雑誌 Volume: 123 Pages: 114-118
  • NAID: 120005568313
  • Peer Reviewed
• [Presentation] Indispensable role of α and β isoforms of class II phosphoinositide 3-kinases (PI3K) in the uterine smooth muscle contraction during labor. (2018)
  • Author(s): Sarker Kabir Azadul, Sho Aki, Kazuaki Yoshioka, Koji Kuno, Yasuo Okamoto, Aung Thuzar Khin, Pham Quynh Hoa, Islam Shahidul, Noriko Takuwa, Yoh Takuwa
  • Organizer: 第 95 回日本生理学会大会
• [Presentation] スフィンゴシン1-リン酸（S1P）2型受容体S1P2による腫瘍血管新生と血管障壁機能の制御 (2017)
  • Author(s): 岡本安雄
  • Organizer: 第27回創薬・薬理フォーラム岡山
  • Invited
• [Presentation] 抗がん剤による臓器障害におけるスフィンゴシン-1-リン酸（S1P）情報伝達系の関与 (2017)
  • Author(s): 多久和 典子、石丸 和宏、岡本 安雄、多久和 陽
  • Organizer: 第27回日本病態生理学会大会
• [Presentation] エイコサペンタエン酸による糖尿病性血管内皮機能障害に対する慢性投与の治療効果および血管への直接作用 (2017)
  • Author(s): 竹之内康広, 坪井一人, 大竹一男, 加園恵三, 岡本安雄
  • Organizer: 第132回日本薬理学会近畿部会
• [Presentation] マウス分娩過程におけるADAMTS-1の役割の解析 (2017)
  • Author(s): 生水 真紀夫、多久和 陽、岡本 安雄、松島 綱治、久野 耕嗣
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Presentation] 脂質メディエーターであるN-アシルエタノールアミンとリゾホスファチジン酸の新規生合成機構 (2017)
  • Author(s): 坪井一人, Rahman Iffat Ara Sonia, Hussain Zahir, 山下量平, 岡本蓉子, 宇山徹, 竹之内康広, 田中保, 岡本安雄, 徳村彰, 上田夏生
  • Organizer: 第28回創薬・薬理フォーラム岡山
• [Presentation] マウス分娩時の子宮機能におけるADAMTS-1の役割の解析 (2016)
  • Author(s): 生水 真紀夫、多久和 陽、岡本 安雄、栗原 裕基、松島 綱治、久野耕司
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜、神奈川県横浜市
  • Year and Date: 2016-12-02
• [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 (2016)
  • Author(s): 安藝 翔、吉岡 和晃、岡本 安雄、多久和 典子、Hoa Quynh Pham、MD Azadul Kabir Sarker、Khin Thuzar Aung、Shahidul Islam、多久和 陽
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜、神奈川県横浜市
  • Year and Date: 2016-12-01
• [Presentation] S1P2, a receptor for the lysophospholipid mediator sphingosine 1-phosphate, protects against vascular barrier disruption. (2016)
  • Author(s): Yasuo Okamoto, Hong Cui, Kazuaki Yoshioka, Noriko Takuwa, Toshishige Shibamoto, Yoh Takuwa
  • Organizer: The 8th Congress of the International Federation of Shock Societies
  • Place of Presentation: Tokyo Dome Hotel, Tokyo, Japan
  • Year and Date: 2016-10-05
  • 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: 金沢医科大学、石川県河北郡内灘町
  • Year and Date: 2016-08-06
• [Presentation] S1P2による血管新生と血管障壁機能の制御 (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: にぎわい交流館AU、秋田県秋田市
  • Year and Date: 2016-06-10
  • Invited
• [Presentation] Sphingosine 1-phosphate (S1P) receptor-2 (S1P2) aggravates lung fibrosis through altering alveolar macrophage polarization and cellular senescence in mice (2016)
  • Author(s): JuanJuan Zhao, Yasuo Okamoto, Kazuaki Yoshioka, Noriko Takuwa, Takashi Wada, Yutaka Inagaki, Chiaki Takahashi, Yoh Takuwa
  • Organizer: 日本生化学会北陸支部第３４回大会
  • Place of Presentation: 金沢大学宝町キャンパス、石川県金沢市
  • Year and Date: 2016-05-28
• [Presentation] PI3K-C2α is required for TGFβ-induced receptor endocytosis and endosomal signaling in endothelia cells (2016)
  • Author(s): Sho Aki, Kazuaki Yoshioka, Yasuo Okamoto, Noriko Takuwa, Yoh Takuwa
  • Organizer: 第93回日本生理学会
  • Place of Presentation: 北海道札幌市
  • Year and Date: 2016-03-22
  • Invited
• [Presentation] Deletion of sphingosine 1-phospahte (S1P) receptor-2 (S1P2) inhibits lung fibrosis through altering alveolar macrophage polarization and senescence in mice (2015)
  • Author(s): Juanjuan 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: 兵庫県神戸市
  • Year and Date: 2015-12-01
• [Presentation] Role of S1P2 in inflammation and fibrosis (2015)
  • Author(s): Yoh Takuwa, Juanjuan Zhao, Yasuo Okamoto, Kazuaki Yoshioka, Noriko Takuwa
  • Organizer: 14 th International Conference on Bioactive Lipids in Cancer, Inflammation, and Related Diseases Plenary Lecture
  • Place of Presentation: ハンガリー ブタペスト
  • Year and Date: 2015-07-12
  • Invited
• [Presentation] Sphingosine 1-phosphate receptor-2 plays a protective role against anaphylaxis and acute lung injury (2015)
  • 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: 石川県片山津
  • Year and Date: 2015-06-16
• [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: 東京都千代田区
  • Year and Date: 2015-05-28
• [Book] Bioactive Lipid Mediators (2015)
  • Author(s): Noriko Takuwa, Yasuo Okamoto, Kazuaki Yoshioka, Yoh Takuwa
  • Total Pages: 426
  • Publisher: Springer Japan
• [Patent(Industrial Property Rights)] マクロファージの増殖・分化阻害又はマクロファージの老化促進による肺線維症の抑制 (2015)
  • Inventor(s): 多久和陽、岡本安雄
  • Industrial Property Rights Holder: 多久和陽、岡本安雄
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2015-137937
  • Filing Date: 2015-07-09