Bioactive lipids as regulators of plasticity of lymphatics
Project/Area Number |
18H02605
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 48030:Pharmacology-related
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Research Institution | Kitasato University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
伊藤 義也 北里大学, 医学部, 講師 (40203187)
天野 英樹 北里大学, 医学部, 教授 (60296481)
細野 加奈子 北里大学, 医学部, 講師 (80532556)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2019: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2018: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
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Keywords | 生理活性資質 / プロスタグランジン / トロンボキサン / 炎症 / 浮腫 / リンパ節転移 / リンパ管新生 / 生理活性脂質 / リンパ流 / TP受容体 / 生理活性ペプチド / 肝障害 / 大腸炎 / 子宮内膜症 / VEGF-C / 腹膜炎 / DSS腸炎 / リンパ浮腫 / 脂質吸収 / LPS / COX-2 / mPHES-1 / プロスタグランジンン / 受容体 / がん転移 / 緑内障 |
Outline of Final Research Achievements |
utilizing peritonitis model, a novel function of TX, the facilitation of lymphangiogenesis via TP signaling was reported using tissue-specific TP knockout mice. Compared with wild-type mice, lipopolysaccharide-induced lymphangiogenesis in systemic TP-knockout mouse diaphragm tissues was suppressed with reduced drainage function from the peritoneal cavity. TP-positive macrophages and T cells accumulated in the diaphragm produced VEGF-C and VEGF-D in a TP-dependent manner. Removal of macrophages and T cells resulted in reduced lymphangiogenesis and lowered expressions of VEGF-C and VEGF-D. TP knockout specific to macrophages and T cells also led to reduced lymphangiogenesis and drainage function in mice with lipopolysaccharide injections. This study suggested that TP signaling exerts prolymphangiogenic activity by acting on macrophages and T cells and that TP signaling represents a novel target for controlling lymphangiogenesis.
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Academic Significance and Societal Importance of the Research Achievements |
一貫して生理活性脂質(アラキドン酸代謝物など)の血管新生、リンパ管新生における役割を解析してきた。これらの物質は、生体内ではそれぞれの受容体に作用して活性を発揮する。遺伝子改変動物を用いて、受容体シグナリングの役割を解析した。血管、リンパ管新生という生命現象は、"炎症"や"がん"など、多彩な病態の進展に関与することを示せたことは意義が大きい。ゴードン会議などで成果を発表し、海外への情報発信を積極的に行ってきた。疾患に悩む患者が恩恵を得なければ意味がないという信念のもと、病態解析に立脚した創薬のシーズを提供することを心掛けてきた。リンパ管新生病態の進展に関与する多くの病態解明に貢献できた。
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Report
(4 results)
Research Products
(25 results)
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[Journal Article] Roles of Thromboxane Receptor Signaling in Enhancement of Lipopolysaccharide-Induced Lymphangiogenesis and Lymphatic Drainage Function in Diaphragm.2021
Author(s)
Matsuda H, Ito Y, Hosono K, Tsuru S, Inoue T, Nakamoto S, Kurashige C, Hirashima M, Narumiya S, Okamoto H, Majima M.
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Journal Title
Arterioscler Thromb Vasc Biol.
Volume: 41
Issue: 4
Pages: 1390-1407
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Microsomal prostaglandin E synthase-1 promotes lung metastasis via SDF-1/CXCR4-mediated recruitment of CD11b+Gr1+MDSCs from bone marrow2020
Author(s)
Takahashi R, Amano H, Ito Y, Eshima K, Satoh T, Iwamura M, Nakamura M, Kitasato H, Uematsu S, Raouf J, Jakobsson PJ, Akira S, Majima M
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Journal Title
Biomedicine & Pharmacotherapy
Volume: 121
Pages: 109581-109581
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Thromboxane A(2) receptor signaling in endothelial cells attenuates monocrotaline-induced liver injury.2019
Author(s)
Otaka F, Ito Y, Inoue T, Ohkubo H, Nishizawa N, Kojo K, Betto T, Yamane S, Narumiya S, Koizumi W, Majima M
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Journal Title
Toxicol Appl Pharmacol
Volume: 381
Pages: 114733-114733
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] VEGF Receptor 1-Expressing Macrophages Recruited from Bone Marrow Enhances Angiogenesis in Endometrial Tissues.2019
Author(s)
Sekiguchi K, Ito Y, Hattori K, Inoue T, Hosono K, Honda M, Numao A, Amano H, Shibuya M, Unno N, Majima M
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Journal Title
Sci Rep
Volume: 7
Issue: 1
Pages: 7037-7037
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Inhibition of microsomal prostaglandin E synthase-1 facilitates liver repair after hepatic injury in mice.2018
Author(s)
Nishizawa N, Ito Y, Eshima K, Ohkubo H, Kojo K, Inoue T, Raouf J, Jakobsson PJ, Uematsu S, Akira S, Narumiya S, Watanabe M, Majima M.
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Journal Title
J Hepatol.
Volume: S0168-8278(18)
Issue: 1
Pages: 30126-30130
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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