FUNCTIONAL INVOLVEMENT OF SCIATIC NERVE-DERIVED VERSICAN AND DECORIN-LIKE MOLECULES AND OTHER CHONDROITIN SULFATE PROTEOGLYCANS IN ECM-MEDIATED CELL-ADHESION AND NEURITE OUTGROWTH
FUNCTIONAL INVOLVEMENT OF SCIATIC NERVE-DERIVED VERSICAN AND DECORIN-LIKE MOLECULES AND OTHER CHONDROITIN SULFATE PROTEOGLYCANS IN ECM-MEDIATED CELL-ADHESION AND NEURITE OUTGROWTH
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DOI：
10.1111/j.1460-9568.1995.tb00683.x
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发表时间：
1995-04-01
影响因子：
3.4
通讯作者：
SCHACHNER, M
中科院分区：
文献类型：
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作者：
BRAUNEWELL, KH;PESHEVA, P;SCHACHNER, M
我们以前已经描述了两种来自人类坐骨神经的蛋白多糖，它们与硫酸软骨素蛋白多糖versican和decorin在免疫化学上相关。先前已经发现，在成年小鼠坐骨神经损伤后，versican样分子的硫酸软骨素和decorin样分子的核心蛋白上调。为了研究花青素和装饰素样分子是否参与细胞-细胞外基质相互作用，我们研究了这两种分子对细胞粘附的影响。与纤维连接蛋白混合，而不与层粘连蛋白或I型或IV型胶原包被的versican和decorin样分子底物抑制了几种细胞系，新生儿背根神经节神经元和雪旺细胞的粘附。抑制活性呈浓度依赖性，并由硫酸软骨素介导。此外，当不同的蛋白聚糖与纤维连接蛋白一起培养时，只有versican-和decorin-like分子以及硫酸软骨素蛋白聚糖聚集蛋白能够抑制纤维连接蛋白介导的细胞粘附，而硫酸肝素蛋白聚糖perlecan则不能。单独包被底物或与纤维连接蛋白或层粘连蛋白混合的versican和decorin样分子对PC12嗜铬细胞瘤细胞和新生儿背根神经节神经元的神经突生长最多有轻微抑制。在固相配体结合实验中，versican-和decorin-like分子与纤维连接蛋白相互作用，但不与层粘连蛋白或I型和IV型胶原相互作用。versican-like分子与纤维连接蛋白的结合和这种分子对细胞粘附的抑制是通过肝素和纤维连接蛋白的细胞结合域介导的。这些观察结果表明，这两种蛋白聚糖与纤维连接蛋白的结合参与了细胞对纤维连接蛋白粘附的调节。
We have previously described two proteoglycans from human sciatic nerve which are immunochemically related to the chondroitin sulphate proteoglycans versican and decorin. The chondroitin sulphate of the versican-like molecule and the core protein of the decorin-like molecule have been found previously to be up-regulated after lesioning the adult mouse sciatic nerve. To investigate if the versican- and decorin-like molecules are involved in cell-extracellular matrix interactions, we studied the effect of both molecules on cell adhesion. The versican- and decorin-like molecules, substrate-coated in a mixture with fibronectin, but not with laminin or collagen types I or IV, inhibited the adhesion of several cell lines, neonatal dorsal root ganglion neurons and Schwann cells. The inhibitory activity was concentration-dependent and mediated by the chondroitin sulphate. Furthermore, when different proteoglycans were incubated with fibronectin, only the versican- and decorin-like molecules and the chondroitin sulphate proteoglycan aggrecan, but not the heparan sulphate proteoglycan perlecan, were able to inhibit fibronectin-mediated cell adhesion. The versican- and decorin-like molecules, substrate-coated alone or in a mixture with fibronectin or laminin, were at most slightly inhibitory to neurite outgrowth from PC12 phaeochromocytoma cells and neonatal dorsal root ganglion neurons. In a solid-phase ligand-binding assay the versican- and decorin-like molecules interacted with fibronectin, but not with laminin or collagen types I and IV, Binding of the versican-like molecule to fibronectin and inhibition of cell adhesion by this molecule was mediated via the heparin and cell-binding domains of fibronectin. These observations suggest that binding of the two proteoglycans to fibronectin is involved in the modulation of adhesion of cells to fibronectin.