Role of TP signaling in enhancement of LPS-induced lymphangiogenesis in a mouse peritonitis model

• Project/Area Number: 15K08241
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Kitasato University
• Principal Investigator: Hosono Kanako 北里大学, 医学部, 非常勤講師 (80532556)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: リンパ管新生 / TP受容体 / 慢性炎症 / ノックアウトマウス

Outline of Final Research Achievements

Lymphatic vessels in diaphragm are essential for draining the inflammatory fluid during peritonitis. In this study, we evaluated role of thromboxane A2 receptor (TP) signaling in enhancement of lymphangiogenesis in peritonitis. Peritonitis was induced by injections of LPS (25μg/mouse) into peritoneal cavities in male C57BL/6 mice. We evaluated lymphatic microvessel density in whole-mounted diaphragm tissues. A week after LPS application, expressions of COX-2, thromboxane synthase (TXS) and VEGF-C/D in diaphragm were up-regulated with increment of lymphangiogenesis, and lymphangiogenesis and the expressions of VEGF-C/D were suppressed in TP KO mice. CD3ε positive cells and CD11b positive cells expressing VEGF-C/D were accumulated in diaphragm in a TP-dependent manner. These results indicated that lymphangiogenesis in diaphragm is up-regulated by TX-TP signaling via induction of VEGF-C/D, suggesting TP signaling as a potential therapeutic target.

Research Products

• [Journal Article] 特集 血管制御系と疾患 生理活性脂質と脈管新生 (2017)
  • Author(s): 馬嶋正隆、天野英樹、細野加奈子、伊藤義也
  • Journal Title: 生体の科学 Volume: 68 Issue: 4 Pages: 304-308
  • DOI: 10.11477/mf.2425200634
  • ISSN: 0370-9531, 1883-5503
  • Year and Date: 2017-08-15
  • Open Access
• [Journal Article] Prostaglandin E Receptors, EP3 and EP4 Facilitates Wound Healing and Lymphangiogenesis with Enhanced Recruitment of M2 Macrophages in Mice. (2016)
  • Author(s): Hosono K, Isonaka R, Kawakami T, Narumiya S, Majima M.
  • Journal Title: PLoS One. Volume: 11 Issue: 10 Pages: e0162532-e0162532
  • DOI: 10.1371/journal.pone.0162532
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Vascular endothelial growth factor receptor type 1 signaling prevents delayed wound healing in diabetes by attenuating the production of IL-1β by recruited macrophages. (2016)
  • Author(s): Okizaki S, Ito Y, Hosono K, Oba K, Ohkubo H, Kojo K, Nishizawa N, Shibuya M, Majima M.
  • Journal Title: Am J Pathol Volume: 186(6) Pages: 1481-1498
  • Peer Reviewed / Open Access
• [Journal Article] Roles of mPGES-1, an inducible prostaglandin E synthase, in enhancement of LPS-induced lymphangiogenesis in a mouse peritonitis model. (2015)
  • Author(s): Matsuda H, Hosono K, Tsuru S, Kurashige C, Sekiguchi K, Akira S, Uematsu S, Okamoto H, Majima M.
  • Journal Title: Life Sci. Volume: 142 Pages: 1-7
  • DOI: 10.1016/j.lfs.2015.10.008
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Thromboxane A2 induces blood flow recovery via platelet adhesion to ischaemic regions. (2015)
  • Author(s): Amano H, Ito Y, Eshima K, Kato S, Ogawa F, Hosono K, Oba K, Tamaki H, Sakagami H, Shibuya M, Narumiya S, Majima M.
  • Journal Title: Cardiovasc Res. Volume: 107 Issue: 4 Pages: 509-521
  • DOI: 10.1093/cvr/cvv139
  • Peer Reviewed / Open Access
• [Journal Article] プロスタグランジンによるリンパ管新生とリンパ組織可塑性の制御 (2015)
  • Author(s): 馬嶋正隆、細野加奈子
  • Journal Title: 医学のあゆみ Volume: 254 Pages: 1109-1114
• [Journal Article] 病態時のリンパ管新生、リンパ組織の可塑性を制御するプロスタノイドの役割 (2015)
  • Author(s): 馬嶋正隆、天野英樹、細野加奈子
  • Journal Title: 細胞 Volume: 47 Pages: 20-23
• [Presentation] 病態時のリンパ管新生を制御する脂質メディエーターの役割 (2017)
  • Author(s): 細野加奈子、松田弘美、馬嶋正隆
  • Organizer: 第41回日本リンパ学会総会
• [Presentation] リンパ管・リンパ組織の可塑性を制御する生理活性脂質の役割 (2016)
  • Author(s): 馬嶋正隆、天野英樹、細野加奈子
  • Organizer: 第40回日本リンパ学会総会
  • Place of Presentation: 東京大学 伊藤国際学術研究センター(東京都文京区)
  • Year and Date: 2016-06-24
  • Invited
• [Presentation] エンドトキシン誘発腹膜炎マウスの横隔膜リンパ管新生を増強するトロンンボキサン受容体シグナリングの役割 (2016)
  • Author(s): 松田弘美，細野加奈子，馬嶋正隆
  • Organizer: 第40回日本リンパ学会総会
  • Place of Presentation: 東京大学 伊藤国際学術研究センター(東京都文京区)
  • Year and Date: 2016-06-24
• [Presentation] Roles of Prostaglandins in regulation of plasticity of lymphatics and lymph nodes (2016)
  • Author(s): Majima Masataka, Hosono Kanako, Amano Hideki, Fujita Tomoe
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: パシフィコ横浜（横浜市西区）
  • Year and Date: 2016-03-09
  • Invited
• [Presentation] Role of TP signaling in enhancement of LPS-induced lymphangiogenesis in a mouse peritonitis model (2016)
  • Author(s): Matsuda Hiromi, Hosono Kanako, Tsuru Seri, Narumiya Shuh, Majima Masataka
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: パシフィコ横浜（横浜市西区）
  • Year and Date: 2016-03-09
• [Presentation] Signaling of prostaglandin E receptors, EP3 and EP4 facilitates wound healing and lymphangiogenesis with enhanced recruitment of CD11b+ macrophages in mice (2016)
  • Author(s): Hosono Kanako, Isonaka Risa , Kawakami Tadashi, Narumiya Shuh, Majima Masataka
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: パシフィコ横浜（横浜市西区）
  • Year and Date: 2016-03-09
• [Book] 実験医学 (2017)
  • Author(s): 馬嶋正隆、天野英樹、細野加奈子
  • Total Pages: 7
  • Publisher: 洋土社
• [Book] 炎症と免疫 (2016)
  • Author(s): 馬嶋正隆、天野英樹、細野加奈子
  • Total Pages: 10
  • Publisher: 先端医学社
• [Remarks] 北里大学医学部薬理学 大学院医療系研究科分子薬理学
  • URL: http://www.med.kitasato-u.ac.jp/pharm/index.html
• [Remarks] 北里大学医学部薬理学 大学院医療系研究科分子薬理学
  • URL: http://www.med.kitasato-u.ac.jp/pharm/index.html