Mechanisms for the regulation of vascular homeostasis by functional lipid molecules
| Project/Area Number |
24390051
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | Kanazawa University |
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Principal Investigator |
TAKUWA Yoh 金沢大学, 医学系, 教授 (60171592)
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| Co-Investigator(Renkei-kenkyūsha) |
OKAMOTO Yasuo 金沢大学, 医学系, 准教授 (80293877)
YOSHIOKA Kazuaki 金沢大学, 医学系, 助教 (80333368)
TAKUWA Noriko 石川県立看護大学, 看護学部, 教授 (70150290)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2014: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2013: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2012: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
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| Keywords | 脂質メディエーター / スフィンゴシンー１－リン酸 / イノシトールリン脂質 / PI3-キナーゼ / シグナル伝達 / 血管新生 / 血管障壁 / 血管医学 / 脂質 / 循環器・高血圧 / 生体分子 / 生理学 / 循環器疾患 |
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| Outline of Final Research Achievements |
We studied the mechanisms by which sphingosine-1-phosphate receptor S1P2 and phosphatidylinositol 3-kinase (PI3K) class II α-isoform (PI3K-C2α). S1P2 in the vascular endothelium protected the vasculature from acute disruption of vascular barrier integrity induced by anaphylactic mediators and lipopolysaccharide. This effect was mediated by S1P2-mediated inhibition of Akt and eNOS. S1P2 decreased the generation of nitric oxide (NO) by eNOS, resulting in inhibition of NO-mediated disruption of adherens junctions. Genetic deletion of PI3K-C2α impaired developmental and pathological angiogenesis. PI3K-C2α was necessary for VE-cadherin transport to the cell-cell junction, VEGF receptor endocytosis and endosomal receptor signaling, through which PI3K-C2α served an essential role in angiogenesis.
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Report
(4 results)
Research Products
(50 results)
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[Journal Article] Selenoprotein P as a diabetes-associated hepatokine that impairs angiogenesis by inducing VEGF resistance in vascular endothelial cells.2014
Author(s)
Ishikura K, Misu H, Kumazaki M, Takayama H, Matsuzawa-Nagata N, Tajima N, Chikamoto K, Lan F, Ando H, Ota T, Sakurai M, Takeshita Y, Kato K, Fujimura A, Miyamoto K, Saito Y, Kameo S, Okamoto Y, Takuwa Y, Takahashi K, Kidoya H, Takakura N, Kaneko S, Takamura T
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Journal Title
Diabetologia
Volume: 57
Issue: 9
Pages: 1968-1976
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
Pharmacology Research & Perspectives
Volume: 2
Issue: 5
Pages: 68-68
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] CCL2/CCR2 augments the production of transforming growth factor-beta1, type 1 collagen and CCL2 by human CD45-/collagen 1-positive cells under high glucose concentrations.2013
Author(s)
Hara A, Sakai N, Furuichi K, Sakai Y, Takeya M, Bucala R, Mukaida N, Takuwa Y, Matsushima K, Kaneko S, Wada T.
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Journal Title
Clin Exp Nephrol.
Volume: 17
Issue: 6
Pages: 793-804
DOI
Related Report
Peer Reviewed
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[Journal Article] Essential role of endothelial class II PI3K-C2αin angiogenesis and vascular barrier function2012
Author(s)
Yoshioka K, Yoshida K, Cui H, Wakayama T, Takuwa N, Okamoto Y, Du W, Qi X, Asanuma K, Sugihara K, Aki S, Miyazawa H, Biswas K, Nagakura C, Ueno M, Iseki S, Schwartz JR, Okamoto H, Sasaki T,Matsui O, Asano M, Adams HR, Takakura N, Takuwa Y.
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Journal Title
Nature med
Volume: 18
Issue: 10
Pages: 1560-1569
DOI
Related Report
Peer Reviewed
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