Platelet-derived growth factor stimulates the formation of Versican-Hyaluronan aggregates and pericellular matrix expansion in arterial smooth muscle cells

Platelet-derived growth factor stimulates the formation of Versican-Hyaluronan aggregates and pericellular matrix expansion in arterial smooth muscle cells
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DOI:
10.1006/abbi.2001.2507
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发表时间:
2001-10-01
影响因子:
3.9
通讯作者:
Wight, TN
Wight, TN
中科院分区:
生物学3区
文献类型:
--
作者:
Evanko, SP;Johnson, PY;Wight, TN

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在增殖和迁移的脱离阶段,动脉平滑肌细胞(ASMC)周围优先形成富含Hybryonan和versican的细胞周基质。PDGF是ASMC的有效促分裂剂和趋化剂,并且还刺激细胞外基质分子的产生,所述细胞外基质分子可调节细胞的增殖和迁移能力。我们研究了PDGF对透明质酸依赖的细胞周基质形成的影响,以及对几种主要细胞周涂层成分的合成和相互作用的影响。如使用颗粒排阻试验所证明的,PDGF刺激细胞周围基质的形成,并且在具有被膜和更大的被膜尺寸的细胞的比例增加中均观察到。这种增加伴随着透明质酸合成酶2(HAS 2)表达的短暂增加以及透明质酸合成和聚合物长度的增加。PDGF还增加了多功能蛋白聚糖和连接蛋白的合成,如在mRNA和蛋白质水平上所测量的。天然多功能蛋白聚糖-透明质酸聚集体和连接稳定的聚集体的量在PDGF处理后也增加。时间推移成像显示,细胞周围的基质形成发生在尾随细胞的过程之前,他们的分离。这些数据表明,PDGF调节ASMC的细胞外被膜形成分子,如多功能蛋白聚糖,透明质酸和连接蛋白的合成和组织,这导致细胞外基质扩张和ASMC表型的改变。(C)北京:科学出版社.
Hyaluronan and versican-rich pericellular matrices form around arterial smooth muscle cells (ASMC) preferentially during the detachment phase of proliferation and migration. PDGF is a potent mitogen and chemotactic agent for ASMC and also stimulates the production of extracellular matrix molecules which may regulate the proliferative and migratory capacity of the cells. We have examined the effect of PDGF on the formation of hyaluronan-dependent pericellular matrices, and on the synthesis and interaction of several major pericellular coat constituents. As demonstrated using a particle exclusion assay, PDGF stimulated the formation of pericellular matrices and was seen both in an increased proportion of cells with a coat and a greater coat size. This increase was accompanied by a transient increase in hyaluronan synthase 2 (HAS2) expression and an increase in hyaluronan synthesis and polymer length. PDGF also increased the synthesis of versican and link protein as measured at the mRNA and protein levels. The amount of native versican-hyaluronan aggregates and link-stabilized aggregate was also increased following PDGF treatment. Time lapse imaging showed that pericellular matrix formation occurred around trailing cell processes prior to their detachment. These data suggest that PDGF modulates the synthesis and organization of ASMC pericellular coat-forming molecules such as versican, hyaluronan, and link protein, which leads to extracellular matrix expansion and alterations in ASMC phenotype. (C) 2001 Academic Press.