| Project/Area Number |
10670657
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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 |
Circulatory organs internal medicine
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| Research Institution | Kobe University School of Medicine |
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Principal Investigator |
ISHIKAWA Yuichi Kobe University School of Medicine, Faculty of Health Science, Professor, 医学部, 教授 (90159707)
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| Co-Investigator(Kenkyū-buntansha) |
KAWASHIMA Seinosuke Kobe University School of Medicine, First Department of Internal Medicine, Associate Professor, 医学部・附属病院, 講師 (10177678)
TANIGUCHI Takahiro Kobe University School of Medicine, First Department of Internal Medicine, Associate Professor, 医学部・附属病院, 講師 (20263379)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1998: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | Leptin / Vascular Smooth Muscle Cells / Proliferation / Migration / Signal Transduction / MAP kinase / PI 3-kinase / 動脈硬化 / 血管形成術後再挟窄 / 細胞増殖 |
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| Research Abstract |
Obesity is one of the major risk factors for cardiovascular diseases. However, less is yet known about the molecular mechanisms associating between obesity and cardiovascular diseases. The ob gene product, leptin has been defined as a regulator of food intake and energy expenditure. The receptors for leptin (OB-R) are widely expressed throughout the body, suggesting that, in addition to the control of food intake and body weight, leptin may have other important physiological functions. In obese patients, plasma leptin levels are elevated. Therefore, in this study, we investigated the effect of leptin on vascular smooth muscle cell (VSMC) functions. Cultured rat aortic VSMC expressed several isoforms of leptin receptors including 130-kDa short form. Leptin stimulated both proliferation and migration of VSMC. Leptin stimulated phosphorylation and activation of extracellular-regulated Kinase (ERK) isoformes of mitogen-activated protein (MAP) kinases, and also increased phosphatidylinositol (PI) 3-kinase activity in anti-phosphotyrosine immunoprecipitates in VSMC. Further, two distinct PI 3-kinase inhibitors, wortmannin and LY294002 inhibited the migratory effect of leptin, indicating the essential role of PI 3-kinase in leptin-stimulated migration of VSMC. These results demonstrate that leptin is a proliferative and migratory factor for VSMC, implying that leptin plays a role in the formation and development of vascular lesions.
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