| Project/Area Number |
11470156
|
|---|
| 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 SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (00215047)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
ARAI Masashi GUNMA UNIVERSITY SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 講師 (60270857)
|
|---|
| Project Period (FY) |
1999 – 2000
|
| Project Status |
Completed (Fiscal Year 2000)
|
| Budget Amount *help |
¥10,300,000 (Direct Cost: ¥10,300,000)
Fiscal Year 2000: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 1999: ¥6,100,000 (Direct Cost: ¥6,100,000)
|
|---|
| Keywords | CARP / TRANSCRIPTION / VASCULAR SMOOTH MUSCLE CELL / TGF-β / PROMOTER / ANKYRIN / SIGNALING / GENE EXPRESSION / ストレス応答 / BTEB2 / Hex / スタチン / エンドセリン / 血管 / 転写 / 心肥大 / 心不全 / SHR / イソプロテノール |
|---|
| Research Abstract |
Despite the pleiotropic effects of TGF-β on vascular smooth muscle cells (VSMCs), only few genes have been characterized as direct targets of TGF-β in VSMCs. CARP, cardiac ankyrin repeat protein, has been thought to be expressed exclusively in the heart. In this study we showed that CARP is expressed in the vasculature after balloon injury and in cultured VSMCs in response to TGF-β. Analysis of a half-life of the cytoplasmic CARP mRNA levels and the transient transfection of the CARP promoter/luciferasere gene indicate that the regulation of CARP expression is increased by TGF-β at the transcriptional level. Transfection of expression vectors encoding Smads significantly activated the CARP promoter/luciferase activity. Deletion analysis and site-specific mutagenesis of the CARP promoter indicate that TGF-β response element is localized to CAGA motif at -108 bp relative to the transcription start site. Electrophoretic mobility shift assays showed that the binding activity to the CAGA motif was increased in nuclear extracts of cultured VSMCs by TGF-β. Cells transfected with adenovirus vector expressing CARP showed a significant decrease in DNA synthesis. Overexpression of CARP enhanced the TGF-β-mediated inhibition of the DNA synthesis. These data indicate that CARP is a downstream target of TGF-β/Smad-signaling in VSMCs, and suggest a role of CARP in mediating the inhibitory effects of TGF-β on the proliferation of VSMCs.
|
