Formation of hyaluronan- and versican-rich pericellular matrix is required for proliferation and migration of vascular smooth muscle cells
Formation of hyaluronan- and versican-rich pericellular matrix is required for proliferation and migration of vascular smooth muscle cells
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DOI：
10.1161/01.atv.19.4.1004
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发表时间：
1999-04-01
影响因子：
8.7
通讯作者：
Wight, TN
中科院分区：
文献类型：
--
作者：
Evanko, SP;Angello, JC;Wight, TN
在动脉粥样硬化的病变中，透明质酸(HA)及其结合蛋白多糖在平滑肌细胞周围的聚集表明，这些分子共同在动脉粥样硬化的形成过程中起着重要的作用。在这项研究中，我们用颗粒排除法检测了体外培养的人主动脉平滑肌细胞形成富含透明质酸和多糖的细胞外基质，以及细胞外基质在细胞增殖和迁移中的作用。透明质酸对细胞周围基质的结构依赖性可以通过链霉菌透明质酸酶完全去除基质来证明。免疫细胞化学方法证实了凡西康存在于细胞周围基质中。在电子显微镜下，细胞被认为是由透明质酸酶敏感的细丝组成的缠绕的网络，上面装饰着Ru红阳性的蛋白多糖颗粒。在受伤的培养物中，90%的迁移细胞，以及几乎所有的有丝分裂细胞，都显示出丰富的透明质酸和富含多糖类物质的外壳。延时视频成像显示，富含透明质酸和万寿菊的细胞周围基质的形成是动态和快速的，并与细胞分离和有丝分裂细胞圆形特异性地协调。HA寡糖抑制HA与细胞表面的结合，阻止细胞周围基质的形成，显著减少了对血小板衍生生长因子的反应，而较大的HA片段和高分子量HA则没有作用。用HA寡糖处理后，细胞形态也发生了变化，从典型的梭形形态转变为更平展和扁平的外观。这些数据表明，富含HA和多糖类的细胞周围基质的组织可能通过减少细胞表面的粘附性，并通过空间排斥和HA蛋白多糖凝胶的粘性性质影响细胞形状，从而促进迁移和有丝分裂。
The accumulation of hyaluronan (HA) and the HA-binding proteoglycan versican around smooth muscle cells in lesions of atherosclerosis suggests that together these molecules play an important role in the events of atherogenesis. In this study we have examined the formation of HA- and versican-rich pericellular matrices by human aortic smooth muscle cells in vitro, using a particle-exclusion assay, and the role of the pericellular matrix in cell proliferation and migration. The structural dependence of the pericellular matrix on HA can be demonstrated by the complete removal of the matrix with Streptomyces hyaluronidase. The presence of versican in the pericellular matrix was confirmed immunocytochemically. By electron microscopy, the cell coat was seen as a tangled network of hyaluronidase-sensitive filaments decorated with ruthenium red-positive proteoglycan granules. Ninety percent of migrating cells in wounded cultures, and virtually all mitotic cells, displayed abundant HA- and versican-rich coats. Time-lapse video imaging revealed that HA- and versican-rich pericellular matrix formation is dynamic and rapid, and coordinated specifically with cell detachment and mitotic cell rounding. HA oligosaccharides, which inhibit the binding of HA to the cell surface and prevent pericellular matrix formation, significantly reduced proliferation and migration in response to platelet-derived growth factor, whereas larger HA fragments and high molecular weight HA had no effect. Treatment with HA oligosaccharides also led to changes in cell shape from a typical fusiform morphology to a more spread and flattened appearance. These data suggest that organization of HA- and versican-rich pericellular matrices may facilitate migration and mitosis by diminishing cell surface adhesivity and affecting cell shape through steric exclusion and the viscous properties of HA proteoglycan gels.