Friedrich Miescher Institute for Biomedical Research, Novartis Research Foundation, Basel, Switzerland.
Int J Biol Sci. 2012;8(2):187-94. doi: 10.7150/ijbs.8.187. Epub 2011 Dec 20.
Tenascins are extracellular matrix glycoproteins associated with cell motility, proliferation and differentiation. Tenascin-C inhibits cell spreading by binding to fibronectin; tenascin-R and tenascin-X also have anti-adhesive properties in vitro. Here we have studied the adhesion modulating properties of the most recently characterized tenascin, tenascin-W. C2C12 cells, a murine myoblast cell line, will form broad lamellipodia with stress fibers and focal adhesion complexes after culture on fibronectin. In contrast, C2C12 cells cultured on tenascin-W fail to spread and form stress fibers or focal adhesion complexes, and instead acquire a multipolar shape with short, actin-tipped pseudopodia. The same stellate morphology is observed when C2C12 cells are cultured on a mixture of fibronectin and tenascin-W, or on fibronectin in the presence of soluble tenascin-W. Tenascin-W combined with fibronectin also inhibits the spreading of mouse embryo fibroblasts when compared with cells cultured on fibronectin alone. The similarity between the adhesion modulating effects of tenascin-W and tenascin-C in vitro led us to study the possibility of tenascin-W compensating for tenascin-C in tenascin-C knockout mice, especially during epidermal wound healing. Dermal fibroblasts harvested from a tenascin-C knockout mouse express tenascin-W, but dermal fibroblasts taken from a wild type mouse do not. However, there is no upregulation of tenascin-W in the dermis of tenascin-C knockout mice, or in the granulation tissue of skin wounds in tenascin-C knockout animals. Similarly, tenascin-X is not upregulated in early wound granulation tissue in the tenascin-C knockout mice. Thus, tenascin-W is able to inhibit cell spreading in vitro and it is upregulated in dermal fibroblasts taken from the tenascin-C knockout mouse, but neither it nor tenascin-X are likely to compensate for missing tenascin-C during wound healing.
纤连蛋白结合蛋白是与细胞运动性、增殖和分化相关的细胞外基质糖蛋白。Tenascin-C 通过与纤维连接蛋白结合抑制细胞铺展；Tenascin-R 和 Tenascin-X 在体外也具有抗黏附特性。在这里，我们研究了最近鉴定的纤连蛋白结合蛋白 Tenascin-W 的黏附调节特性。在纤维连接蛋白上培养的 C2C12 细胞，是一种鼠成肌细胞系，会形成带有应力纤维和焦点粘附复合物的宽片状伪足。相比之下，在 Tenascin-W 上培养的 C2C12 细胞无法铺展，也不会形成应力纤维或焦点粘附复合物，而是获得具有短、带有肌动蛋白尖端的伪足的多极形状。当 C2C12 细胞在纤维连接蛋白和 Tenascin-W 的混合物上培养时，或者在存在可溶性 Tenascin-W 的情况下在纤维连接蛋白上培养时，也会观察到相同的星状形态。与单独在纤维连接蛋白上培养的细胞相比，Tenascin-W 与纤维连接蛋白结合也抑制了小鼠胚胎成纤维细胞的铺展。Tenascin-W 和 Tenascin-C 在体外的黏附调节作用相似，这促使我们研究 Tenascin-W 是否可以在 Tenascin-C 敲除小鼠中补偿 Tenascin-C，特别是在表皮伤口愈合过程中。从 Tenascin-C 敲除小鼠中收获的真皮成纤维细胞表达 Tenascin-W，但从野生型小鼠中收获的真皮成纤维细胞不表达。然而，Tenascin-C 敲除小鼠的真皮中没有上调 Tenascin-W，也没有在 Tenascin-C 敲除动物的皮肤伤口肉芽组织中上调。同样，Tenascin-X 也没有在 Tenascin-C 敲除小鼠的早期伤口肉芽组织中上调。因此，Tenascin-W 能够在体外抑制细胞铺展，并且在从 Tenascin-C 敲除小鼠中获取的真皮成纤维细胞中上调，但无论是 Tenascin-W 还是 Tenascin-X，在伤口愈合过程中都不太可能补偿缺失的 Tenascin-C。
