| Project/Area Number |
11694307
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B).
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Metabolomics
|
|---|
| Research Institution | Osaka City University |
|---|
Principal Investigator |
KOYAMA Hidenori Osaka City University, Medicine, Res Assoc, 医学部, 助手 (80301852)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
NISHIZAWA Yoshiki Osaka City University, Medicine, Professor, 医学部, 教授 (00128745)
SHIOI Atsushi Osaka City University, Medicine, Lecturer, 医学部, 講師 (90260801)
|
|---|
| Project Period (FY) |
1999 – 2000
|
| Project Status |
Completed (Fiscal Year 2000)
|
| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
|
|---|
| Keywords | extracellular matrix / thrombospondin / alpha v beta 3 integrin / atherosclerosis / gene expression / actinin / arterial balloon injury / αvβ_3インテグリン / フィブロネクチン / 細胞遊走 / Subtraction cloning |
|---|
| Research Abstract |
Proliferation and αvβ3 integrin-dependent cell migration of vascular smooth muscle cells are suppressed on polymerized type I collagen. To identify genes specifically regulated in human smooth muscle cells by polymerized collagen, we used the suppressive subtraction hybridization technique. As compared with smooth muscle cells cultured on monomer collagen, polymerized collagen suppresses : 1. a number of other extracellular matrix proteins, including fibronectin, thrombospondin-1, tenascin-C, and cysteine-rich protein 61 ; 2. actin-binding proteins including α-actinin ; 3. signaling molecules ; 4. protein synthesis-associated proteins ; and 5. genes with unknown functions. Some of the identified genes, including cysteine-rich protein 61, show unique kinetics of mRNA regulation by monomer or polymerized collagen distinct from growth factors, suggesting extracellular matrix-specific gene modulation. Moreover, in vivo balloon catheter-mediated injury to the rat carotid artery induces many of the genes that are suppressed by polymerized collagen. Protein levels of thrombospondin-1 and fibronectin are also suppressed by polymerized collagen. Thrombospondin-1-mediated SMC migration on vitronectin is significantly inhibited after culture on polymerized collagen for 24 hours, which is associated with decreased α-actinin accumulation at focal adhesions. Thus, polymerized type I collagen dynamically regulates gene expression, pericellular accumulation of extracellular matrix molecules, and the response to a given matrix molecule.
|
