2006 Fiscal Year Final Research Report Summary
Cross-talk between S1P and VEGF in cutaneous vascular maturation, and its relationship to pathogenesis of psoriasis
| Project/Area Number |
16591101
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Kagawa University |
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Principal Investigator |
KUBOTA Yasuo Kagawa University, Falucity of Medicine, Professor, 医学部, 教授 (10126047)
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| Co-Investigator(Kenkyū-buntansha) |
IGARASHI Junsuke Kagawa University, Falucity of Medicine, Assistant Professor, 医学部, 助教授 (20346638)
KOSAKA Hiroaki Kagawa University, Falucity of Medicine, Professor, 医学部, 教授 (60158897)
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| Project Period (FY) |
2004 – 2006
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| Keywords | apoptosis / platelet / lipid / vascular endothelial cell |
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| Research Abstract |
Sphingosine 1-phosphate (S1P) is a platelet-derived lipid mediator that modulates a wide array of vascular functions, including regulation of blood pressure, cellular proliferation and angiogenic responses via G-protein coupled S1P_1 receptors. In various pathophysiological conditions including psoriasis, oxidative stress exerts deleterious effects on blood vessels, associated with endothelial apoptosis.. We therefore explored whether or not S1P modulates H_2O_2-induced apoptotic responses in cultured bovine aortic endothelial cells (BAEC). BAEC exhibit apoptosis when treated with H_2O_2 (750 μM, for 6 hours), as determined by TUNEL assay (3.5 fold increase of positively stained cells vs. control) and by Cell Death Detection Kit (10.7 fold). H2O2 also promotes cleavage of caspase-3 protein (immunoblot analysis using a subtype-specific antibody, 2.9 fold increase vs. control), a major executor molecule of apoptotic cell death in various cell types, suggesting that oxidative stress promotes apoptosis of BAEC via the caspase-3 pathway. Importantly, when cells have been pre-treated with S1P (1 μM for 30 min) prior to H_2O_2, H_2O_2-induced increases in the numbers TUNEL positive cell as well as the degrees of caspase-3 cleavage are alike attenuated (by 50 and 77 % vs. cells treated by H_2O_2 alone, p < 0.05 respectively). Collectively, these data suggest that a platelet-derived lipid growth factor SIP may protect vascular endothelial cells from oxidative stress-induced apoptotic cell death, possibly representing novel actions of this bioactive lipid on vasculature during wound healing processes.
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Research Products
(2 results)
