Literature DB >> 12377732

Fibrillar collagen regulation of plasminogen activator inhibitor-1 is involved in altered smooth muscle cell migration.

Shinji Tanaka1, Hidenori Koyama, Takuya Ichii, Atsushi Shioi, Masayuki Hosoi, Elaine W Raines, Yoshiki Nishizawa.   

Abstract

OBJECTIVE: Vascular smooth muscle cells (SMCs) cultured on polymerized type I collagen fibrils are arrested in the G1 phase of the cell cycle, and their phenotypic markers and pattern of expressed genes are markedly altered. In this study, we examined polymerized collagen regulation of plasminogen activator inhibitor (PAI)-1 and its involvement in SMC migration. METHODS AND
RESULTS: We demonstrate that secretion and cell surface accumulation of PAI-1 are suppressed in SMCs cultured on polymerized collagen compared with SMCs cultured on monomer collagen. SMCs replated on vitronectin after culture on monomer collagen result in PAI-1 accumulation at focal adhesions and colocalization with alpha(v)beta3 integrins. In contrast, polymerized collagen inhibits PAI-1 accumulation at focal adhesions when the SMCs are replated on vitronectin. Furthermore, for SMCs cultured on polymerized collagen, platelet-derived growth factor-stimulated migration on vitronectin is enhanced by PAI-1, with its function counteracted by urinary plasminogen activator. Finally, exogenous addition of PAI-1 appears to partly restore platelet-derived growth factor-stimulated alpha(v)beta3-dependent SMC migration that is specifically suppressed by polymerized collagen.
CONCLUSIONS: Polymerized type I collagen fibrils dynamically regulate PAI-1, which may be involved in altered alpha(v)beta3 integrin-dependent SMC migration.

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Year:  2002        PMID: 12377732     DOI: 10.1161/01.atv.0000028002.60919.4d

Source DB:  PubMed          Journal:  Arterioscler Thromb Vasc Biol        ISSN: 1079-5642            Impact factor:   8.311


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  4 in total

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