2000 Fiscal Year Final Research Report Summary
Integrin regulation of vascular smooth muscle cell migration
| Project/Area Number |
11838014
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Institution | Osaka City University |
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Principal Investigator |
KOYAMA Hidenori Osaka City University, Medicine, Osaka City University Res Assoc, 医学部, 助手 (80301852)
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| Project Period (FY) |
1999 – 2000
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| Keywords | atherosclerosis / plasminogen activator inhibitor-1(PAI-1) / plasminogen activator (uPA) / uPA receptor (uPAR) / PDGF / alpha v beta 3 integrin / collagen type I |
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| Research Abstract |
Smooth muscle cell (SMC) migration from the medial layer of vessels into forming lesions contributes to atherogenesis. In this study, we demonstrate that SMC culture on polymerized collagen, in contrast with culture on monomer collagen, significantly inhibits αvβ3-dependent SMC migration on vitronectin or osteopontin, but does not alter migration on type I collagen or fibronectin. After culture on polymerized collagen, αvβ3 integrin clustering in focal adhesions on vitronectin is suppressed without a significant change in extracellular expression of αvβ3. Following culture on monomer collagen and plating on vitronectin, plasminogen activator inhibitor-1 (PAI-1) co-localizes with αvβ3 and a blocking PAI-1 antibody inhibits SMC migration. In contrast, polymerized collagen culture suppresses PAI-1 secretion and its accumulation at focal adhesions, while urinary plasminogen activator (uPA) secretion and uPA receptor (uPAR) expression are stimulated. Suppression of SMC migration on vitronectin by polymerized collagen is restored by addition of exogenous PAI-1 protein but not by latent inactive PAI-1, and the effects of PAI-1 are blocked by co-treatment of the SMC with uPA.Finally active PAI-1, but not latent inactive PAI-1, colocalizes with αvβ3 integrin, and blocking antibody for αvβ3 inhibits SMC adhesion to PAI-1. Thus, polymerized collagen appears to dynamically regulate SMC migratory response through modulation of αvβ3 integrin function and the uPA-uPAR-PAI-1 system.
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Research Products
(4 results)
