| Project/Area Number |
14570690
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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 | Jichi Medical School |
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Principal Investigator |
UEBA Hiroto Jichi Medical School, Department of Internal Medicine, Instructor, 医学部, 助手 (80316546)
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| Co-Investigator(Kenkyū-buntansha) |
KAWAKAMI Masanobu Jichi Medical School, Department of Internal Medicine, Professor, 医学部, 教授 (40161286)
KUROKI Masatoshi Jichi Medical School, Department of Internal Medicine, Associate Professor, 医学部, 助教授 (90215096)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | vascular endothelial cells / monocyte / apoptosis / atherpsclerosis / gene cloning |
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| Research Abstract |
Apoptosis of vascular endothelial cells (EC) and monocyte-EC interaction play a critical role in the development and progression of atherosclerosis. We have found that adhesion of monocyte to EC inhibits BC apoptosis. However, the mechanism by which BC apoptosis is regulated remains to be elucidated. In the present study, we analyzed antiapoptotic genes induced in BC by monocyte adhesion using THP-1, a human monocytic cell line and human umbilical vein endothelial cells (HUVEC). Apoptosis of HUVEC was induced by serum starvation arid examined by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) labeling and caspase-3 activity assay. Apoptosis of. HUVEC was significantly inhibited by THP-1 adhesion. mRNAs were isolated from HUVEC cultured with or without THP-1, and genes induced in HUVEC by THP-1 adhesion were analyzed using a DNA microarray (IntelliGene HS Human Expression CHIP, TAKARA BIO). Adhesion of THP-1 to HUVEC induced expression of many kinds of genes in HUVEC including osteopontin, IL-1, selectin B, PPARgamma, and MCP-1 as well as apoptosis-relaled genes such as bcl-2, caspace-8 and BIK. Among these genes expressed, osteopontin was most prominently upregulated by THP-1 adhesion (558-fold increase). Because osteopontin has been reported to play a role in survival pathways related. to cell adhesion, our data provide a novel insight into the genetic mechanism of inhibition of EC apoptosis induced by monocyte adhesion.
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