| Project/Area Number |
06836015
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
血管生物学
|
|---|
| Research Institution | TOHOKU UNIVERSITY (1995)
大分医科大学 (1994) |
|---|
Principal Investigator |
SATO Yasufumi Tohoku University, Institute of Development, Aging and Cancer, Department of Vascular Reserach, Professor, 加齢医学研究所, 教授 (50178779)
|
|---|
| Project Period (FY) |
1994 – 1995
|
| Project Status |
Completed (Fiscal Year 1995)
|
| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1995: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1994: ¥1,400,000 (Direct Cost: ¥1,400,000)
|
|---|
| Keywords | latent TGF-beta / binding / activation / LAP / smooth muscle cell / u-PA / u-PA receptor / 合成ペプチド / 内皮細胞 / モノクローナル抗体 / uPA / uPA受容体 |
|---|
| Research Abstract |
TGF-beta is one of the most important cytokines affecting the course of vascular diseases including atherosclerosis. Since TGF-beta is always secreted in a latent from, the activation of latent TGF-beta after secretion is the crucial step expressing its activity. The present investigator has previously found that latent TGF-beta is activated when endothelial cells (ECs) and smooth muscle cells (SMCs) are in contact. This activation requires u-PA-plasmin activities expressed on ECs and latent TGF-beta bound to SMCs. Since SMCs are not always in contact with ECs in the vascular wall, a mechanism for the activation of latent TGF-beta in homotypic SMCs needs to be elucidated.
The present study revealed that SMCs expressed urokinase-type PA (u-PA) receptor on the cell surface. When exogenous u-PA was added to SMC cultures, u-PA bound to the receptor and expressed its activity on the cell surface. Under this condition, latent TGF-beta was efficiently activated. This effect of u-PA on the activatipn of latent TGF-beta was abrogated by the monoclonal antibody against latency-assosiated peptide (LAP) ; KM-704, which inhibits the binding of latent TGF-beta to SMCs. These results indicate that the simultaneous bindings of u-PA and latent TGF-beta generates active TGF-beta in homotypic SMCs. The binding property of lanent TGF-beta to SMCs was further characterized. The epitope of KM-704 was found to be located on the N-terminal region of LAP consisted with about 80 amino acids. There is not any known sequences for protein-protein interaction in this region. Thus, latent TGF-beta binds to SMC via a novel binding site to LAP.
|
