Tanaka Shinji, Koyama Hidenori, Ichii Takuya, Shioi Atsushi, Hosoi Masayuki, Raines Elaine W, Nishizawa Yoshiki
Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
Arterioscler Thromb Vasc Biol. 2002 Oct 1;22(10):1573-8. doi: 10.1161/01.atv.0000028002.60919.4d.
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.
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.
Polymerized type I collagen fibrils dynamically regulate PAI-1, which may be involved in altered alpha(v)beta3 integrin-dependent SMC migration.
在聚合的I型胶原纤维上培养的血管平滑肌细胞（SMC）停滞于细胞周期的G1期，其表型标志物和基因表达模式发生显著改变。在本研究中，我们检测了聚合胶原对纤溶酶原激活物抑制剂（PAI）-1的调控及其在SMC迁移中的作用。
我们证明，与在单体胶原上培养的SMC相比，在聚合胶原上培养的SMC中PAI-1的分泌和细胞表面积累受到抑制。在单体胶原上培养后重新接种到玻连蛋白上的SMC会导致PAI-1在粘着斑处积累并与α（v）β3整合素共定位。相反，当SMC重新接种到玻连蛋白上时，聚合胶原会抑制PAI-1在粘着斑处的积累。此外，对于在聚合胶原上培养的SMC，PAI-1可增强血小板衍生生长因子刺激的在玻连蛋白上迁移，而尿纤溶酶原激活剂可抵消其功能。最后，外源性添加PAI-1似乎部分恢复了血小板衍生生长因子刺激的α（v）β3依赖性SMC迁移，而这种迁移被聚合胶原特异性抑制。
聚合的I型胶原纤维动态调节PAI-1，这可能参与了α（v）β3整合素依赖性SMC迁移的改变。
