| Project/Area Number |
17590917
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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 |
Metabolomics
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| Research Institution | Chiba University |
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Principal Investigator |
BUJO Hideaki Graduate School of Medicine Chiba University, Department of Genome Research and Clinical Application(M6), Professor, 大学院医学研究院, 教授 (80291300)
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| Co-Investigator(Kenkyū-buntansha) |
UNOKI Hiroyuki Graduate School of Medicine Chiba University, Division of Applied Translational Research, Instructor, 大学院医学研究院, 助手 (40323290)
SAITO Yasushi Graduate School of Medicine Chiba University, Department of Clinical Cell Biology, Professor, 大学院医学研究院, 教授 (50101358)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Arteriosclerosis / Smooth muscle cell / Blood vessel / Migration / Differentiation |
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| Research Abstract |
The aim of study is to clarify the molecular mechanism of LR11, a gene specifically expressed in intimal SMCs, in the development of atherosclerosis.
1. Establishment and characterization of LR11 knockout mice.
The exon 1 of LR11 gene was replaced by NEO gene. The birth and growth properties of LR11-/- mice did not show any obvious difference from those of LR11+/+ mice. The intimal thickness after cuff injury in LR11-/- mice was significantly reduced compared with that in LR11+/+ mice. The cultured LR11-/- SMCs showed a significant decrease in migration activity under PDGF-BB stimulation compared with the LR11+/+ SMCs,
2. The functional analyses of secreted soluble form of LR11
A secreted soluble form of LR11 was established by the deletion of membrane-spanning and intracellular regions. The soluble form showed the inducing activity for migration, attachment and lipd incorporation of cultured macrophages, in addition to the migration activity of SMCs.
3. Regulation of LR11 gene in SMCs.
The LR11 gene transcription was significantly increased by PDGF-BB, and the increased transcription was inhibited by the treatment of pitavastatin. The LR11-overexpressing SMCs showed the decreased response to pitavastatin for migration activity.
These results show that the aim of study could be almost completed in the study years.
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