2003 Fiscal Year Final Research Report Summary
Functional Analysis of p53-Regulatory Protein CARP in Atherosclerosis
| Project/Area Number |
14370218
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Circulatory organs internal medicine
|
|---|
| Research Institution | Gunma University |
|---|
Principal Investigator |
KURABAYASHI Masahiko Gunma University, Medicine, Professor, 医学部, 教授 (00215047)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
ARAI Masashi Gunma University, Medicine, Assistant Professor, 医学部, 講師 (60270857)
|
|---|
| Project Period (FY) |
2002 – 2003
|
| Keywords | CARP / SRF / TGFβ / atherosclerosis / gene expression / transcription factor / p53 / smooth muscle cell |
|---|
| 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.
|
