| Project/Area Number |
05557040
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Gunma University School of Medicine (1995)
The University of Tokyo (1993-1994) |
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Principal Investigator |
NAGAI Ryozo Gunma University School of Medicine 2nd Dept of Int Med, Professor, 医学部, 教授 (60207975)
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| Co-Investigator(Kenkyū-buntansha) |
NABESHIMA Youich National Neuroscience Center, Director, 神経センター, 部長 (60108024)
KURO-O Makoto National Neuroscience Center, research fellow, 神経研究所, 研究員
ARAI Masashi Gunma University School of Medicine 2nd Dept of Int Med, Assistant, 医学部, 助手 (60270857)
花岡 和則 国立精神神経センター, 発生工学, 室長 (40189577)
中原 賢一 東京大学, 医学部(病), 医員
西村 敬史 東京大学, 医学部(病), 医員
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| Project Period (FY) |
1993 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 1995: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1994: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1993: ¥8,300,000 (Direct Cost: ¥8,300,000)
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| Keywords | SMOOTH MUSCLE, / MYOSIN, / SM1 / 2 GENE, / ATHEROSCLEROSIS, / TRANSGENIC MOUSE, / AORTIC DISSECTION, / AGING, / IMMUNOASSAY / 解離性大同脈瘤 / 血管障害 / 大動脈解離 / ミオシン重鎖 / 遺伝子転写 / 血管平滑筋 / SMemb / プロモーター / 遺伝子導入 |
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| Research Abstract |
We previously demonstrated that rabbit and rat smooth muscles contain at least three types of MHCs ; SM1 (204kDa), SM2 (200kDa) and SMemb (200kDa). SM1 and SM2 are two smooth muscle specific MHC isoforms arising from a single gene, and SMemb is a third type of MHC isoform abundantly expressed in embryonic aortas. The expression of three MHC isoforms is developmentallyregulated.
The presence of developmentallyregulated MHC isoforms in vascular smooth muscles provides importantmoleculartools to investigate the molecularmechanism underlying vascular diseases. We first developed an immunoassay for smooth muscle myosin heavy chain isoform (SM1) which could be released into circulation following vascular injury. This assay is sensitive and specific enough to detect circulating SM1 after acute aortic dissection in clincal cases. The sensitivity and specificity of our SM1 assay for diagnosis of aortic dissection were 87% and 97%, respectively.
In order to understand the molecular mechanisms underlying smooth muscle de-differentiation and proliferation occurring in atherosclerosis and restenosis, we characterized the promoter region of the SMemb gene. In this study, we identified a cis element and a transcription factor, BTEB-2, which coordinately regulate the SMemb gene.
We furthemore developed a transgenic mouse in which a single gene was coincidentally knocked out, which resulted in accelerated aging process including atheosclerois, pulmonary emphysema and reduced insulin secretion.
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