Decorin inhibits endothelial migration and tube-like structure formation: Role of thrombospondin-1
Decorin inhibits endothelial migration and tube-like structure formation: Role of thrombospondin-1
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DOI：
10.1006/mvre.2001.2311
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发表时间：
2001-07-01
影响因子：
3.1
通讯作者：
Boucher, Y
中科院分区：
文献类型：
--
作者：
Davies, CD;Melder, RJ;Boucher, Y
内皮细胞受体和细胞外基质（ECM）之间的相互作用在血管生成中起着关键的，但知之甚少的作用。基于核心蛋白聚糖的抗粘附作用，我们假设核心蛋白聚糖与ECM分子如血小板反应蛋白-1（TSP-1）的结合在内皮管状结构（TLS）形成中起调节作用。为了检验这一假设，将内皮细胞铺在TSP-1、核心蛋白聚糖或TSP-1加核心蛋白聚糖的混合底物上。TLS的形成诱导应用I型胶原融合的内皮细胞单层。卡拉胶核心蛋白聚糖以浓度依赖性方式抑制TLSs的形成。在高核心蛋白聚糖浓度（2.5和5.0 μ g/cm（2））的底物上，TLS的减少是由于粘附细胞数量的减少或细胞迁移的减少。在低浓度（0.05和0.25 μ g/cm 2）时，TLS的减少与附着细胞的数量无关。延时视频显微镜显示，核心蛋白聚糖底物促进了同型聚集和孤立索的形成，但牺牲了内皮细胞迁移和TLS的形成。与减少的迁移一致，内皮细胞在核心蛋白聚糖底物上形成较少的粘着斑蛋白阳性的粘着斑和肌动蛋白应力纤维。皮肤核心蛋白聚糖和软骨核心蛋白聚糖的蛋白质核心也显著抑制内皮细胞迁移和TLS形成。TSP-1增强了软骨核心蛋白聚糖的蛋白核心对TLS形成的抑制作用。这些发现表明，核心蛋白聚糖单独或与TSP-1组合干扰ECM分子对内皮细胞受体的激活，从而阻断诱导细胞骨架重组、迁移和TLS形成的细胞内信号，（C）2001 Academic Press。
Interactions between endothelial cell receptors and the extracellular matrix (ECM) play a critical, yet poorly understood role in angiogenesis. Based on the anti-adhesive role of decorin, we hypothesized that decorin binding to ECM molecules such as thrombospondin-1 (TSP-1) plays a regulatory role in endothelial tube-like structure (TLS) formation. To test this hypothesis, endothelial cells were plated on TSP-1, decorin, or mixed substrates of TSP-1 plus decorin. TLS formation was induced by applying type I collagen on the confluent endothelial monolayer. Cartilage decorin inhibited the formation of TLSs in a concentration-dependent manner. On substrates of high decorin concentrations (2.5 and 5.0 mug/cm(2)) the reduction in TLSs was due either to a reduction in the number of adhering cells or to decreased cell migration. At low decorin concentrations (0.05 and 0.25 mug/cm(2)) the reduction in TLSs was independent of the number of attached cells, Time-lapse video microscopy revealed that decorin substrates facilitated homotypic aggregation and isolated cord formation at the expense of endothelial migration and TLS formation. Consistent with the reduced migration, endothelial cells formed fewer vinculin-positive focal adhesions and actin-stress fibers on decorin substrates. Endothelial migration and TLS formation were also significantly inhibited by skin decorin and the protein core of cartilage decorin. The inhibition of TLS formation by the protein core of cartilage decorin was potentiated by TSP-1. These findings suggest that decorin alone or in combination with TSP-1 interferes with the activation of endothelial cell receptors by ECM molecules, thus blocking intracellular signals that induce cytoskeletal reorganization, migration, and TLS formation, (C) 2001 Academic Press.