| Project/Area Number |
14370218
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Gunma University |
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Principal Investigator |
KURABAYASHI Masahiko Gunma University, Medicine, Professor, 医学部, 教授 (00215047)
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| Co-Investigator(Kenkyū-buntansha) |
ARAI Masashi Gunma University, Medicine, Assistant Professor, 医学部, 講師 (60270857)
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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 |
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2003: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2002: ¥8,500,000 (Direct Cost: ¥8,500,000)
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| Keywords | CARP / SRF / TGFβ / atherosclerosis / gene expression / transcription factor / p53 / smooth muscle cell / コファクター / p21 / アンキリン / アデノウイルス / アポトーシス |
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| Research Abstract |
TGF-β plays a major role in the development of vascular diseases. Despite the pleiotropic effects of TGF-b on vascular smooth muscle cells (VSMCs), only few genes have been characterized as direct targets of TGF-β in VSMCs. In this study we showed that CARP is expressed in neointimal SMCs after balloon injury and in cultured VSMCs in response to TGF-β. The CARP gene expression is increased by TGF-β at the transcriptional level. Transfection of expression vectors encoding Smads significantly activated the CARP promoter/luciferase activity. Cells transfected with adenovirus vector expressing CARP showed a significant decrease in DNA synthesis. Overexpression of CARP enhanced the TGF-β-mediated the inhibition of the DNA synthesis. These data indicate that CARP is a downstream target of TGF-β/Smad-signalings in VSMCs, and suggest a role for mediating the inhibitory effects of TGF-β on the proliferation of VSMCs. We also investigated the effects of CARP on the SMC gene expression in the pluripotent 10T1/2 cells and in vascular SMC. The results demonstrated that TGFb1 induces CArG-dependent SM22α gene expression via an increase in SRF expression, and Src-family of tyrosine kinase is important for this effect. Furthermore, CARP overexpression enhanced TGF-β1-induced SM22α gene expression without affecting SRF expression. These findings shed light on the role of CARP for modulating SMC gene expression during development and in vascular disease.
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