2006 Fiscal Year Final Research Report Summary
Interrated research on the physiological role ofbioactive sphingosine-1-phosphate and Edg receptors by using genetically engineered maice.
| Project/Area Number |
17390054
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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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 Yho Kanazawa University, Graduate School of Medical Science, Professor, 医学系研究科, 教授 (60171592)
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| Co-Investigator(Kenkyū-buntansha) |
SUGIMOTO Naotoshi Kanazawa University, Graduate School of Medical Sdenoe, Associate Professor, 医学系研究科, 助教授 (80272954)
YOSHIOKA Kazuaki Kanazawa University, Graduate School of Medical Science, Research Associate, 医学系研究科, 助手 (80333368)
TAKUWA Noriko Ishikawa Prefectural nursing University, Professor, 看護学部, 教授 (70150290)
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| Project Period (FY) |
2005 – 2006
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| Keywords | sphingosine-1-phosphate / Edg / cell motility / Rac / Rho |
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| Research Abstract |
We investigated physiological and pathophysiological roles of sphingosine-l-phosphate (S1P) and its receptors in the cardiovascular system and tumor progression. Slp exerts its pleiotropic effects through acting on the Edg family receptors. The mice that is null for the S1P receptor Edg5 exhibits hypotension compared with wild type littermates. The Edg5-knockout (Edg5-KO) mice showed similar extents of pressor responses to angiotensin II, ACTH, and the nitric oxide synthase inhibitor L-NAME, as the wild type mice. In the murine hindlimb ischemic model due to femoral artery ligation, daily local intramuscular injection into the ischemic limb promoted the recovery of the blood flow with a concomitant increase in the capillary density in the ischemic limb. The PLGA-based slow-releasing S1P that we invented was also effective in stimulating the blood flow recovery. We also found that the mice transgenic for the S1P-synthesizing enzyme sphingosine kinase-1 showed stimulated recovery in the post-ischemic blood flow. In the in vitro capillary-like tube formation assay, the anti-migratory receptor Edg5 inhibited tube formation, and the blockade of Edg5 stimulated tube formation. Thus, Edg5 is likely anti-angiogenic receptor. Edgl is expressed in cardiomyocytes, however, its role is not known. We found that the mice transgenic for Edgl exhibited cardiac hypertrophy, which was prevented by an AT1 receptor antagonist. In the murine tail vein injection model, an Edgl agonist stimulated lung metastasis of B16 melanoma cells probably through acting on Edgl in the host tissues. These results collectively indicate that S1P-Edg system plays important roles in the cardiovascular homeostasis and the cardiovascular and tumor pathophysiology, and suggest potential usefulness of novel therapeutic strategy to target the S1P-Edg system.
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Research Products
(37 results)
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[Journal Article] Takuwa Class II phosphoinositide 3-kinase alfa-isoform regulates Rho, myosin phosphatase and contraction in vascular smooth muscle.2006
Author(s)
Y.Wang, K.Yoshioka, MA.Azam, N.Takuwa, S.Sakurada, Y.Kayaba, N.sugimoto, I.Inoki, T.Kimura, T.Kuwai, Y.
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Journal Title
Biochem J 394
Pages: 581-592
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Statins suppress oxidized low-density lipoprotein-induced macrophage proliferation by inactivation of small G protein-p38 MAPK pathway.2005
Author(s)
T.Senokuchi, T.Matsumura, M.Sakai, M.Yano, T.Taguchi, K.Sonoda, D.Kukidome, K.Imoto, T.Nishikawa, S.Kim-Mitsuyama, Y.Takuwa, E.Araki.
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Journal Title
J. Biol. Chem. Feb 25;280(8)
Pages: 6627-6633
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Maruyama. Thrombin-induced rapid geranylgeranylation of RhoA as an essential process for RhoA activation in endothelial cells.2005
Author(s)
H.Ohkawara, T.Ishibashi, T.Sakamoto, K.Sugimoto, K.Nagata, K.Yokoyama, N.Sakamoto, M.Kamioka, I.Matsuoka, S.Fukuhara, N.Sugimoto, Y.Takuwa, Y.
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Journal Title
J Biol Chem. 18;280(11)
Pages: 10182-10188
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Eguchi Signal-Crosstalk between Rho/ROCK and JNK mediates Migration of Vascular Smooth Muscle Cells stimulated by Angiotensin.2005
Author(s)
H.Ohtsu, M.Mifune, G.D.Frank, S.Saito, T.Inagami, S.K.Mitsuyama, Y.Takuwa, T.Sasaki, J.D.Rothstein, H.Suzuki, H.Nakashima, E.A.Woolfolk, E.D.Motley, S.
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Journal Title
Arterioscler Thromb Vasc Biol. 25
Pages: 1831-1836
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Maruyama Endogenous NO Blockade Enhances Tissue Factor Expression via Increased Ca2+ Influx through MCP-1 in Endothelial Cells by Monocyte Adhesion.2005
Author(s)
T.Sakamoto, T.Ishibashi, N.Sakamoto, K.Sugimoto, K.Egashira H.Ohkawara, K.Nagata, K.Yokoyama, M.Kamioka, T.Ichiki, N.Sugimoto, M.Kurabayashi, K.Suzuki, Y.Takuwa, Y.
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Journal Title
Arterioscler Thromb Vasc Biol. 25(9)
Pages: 2005-2011
Description
「研究成果報告書概要(欧文)」より
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