Sensory neurite outgrowth on white matter astrocytes is influenced by intracellular and extracellular S100A4 protein
Sensory neurite outgrowth on white matter astrocytes is influenced by intracellular and extracellular S100A4 protein
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DOI：
10.1002/jnr.20743
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发表时间：
2006-03-01
影响因子：
4.2
通讯作者：
Kozlova, EN
中科院分区：
文献类型：
--
作者：
Fang, Z;Forslund, N;Kozlova, EN
中枢神经系统（CNS）被认为是轴突再生的非许可环境，因为髓鞘和相关排斥分子的存在。然而，移植到CNS的神经细胞优选在白色物质区域中迁移和延伸其纤维。我们先前的研究表明，白色星形胶质细胞在体内表达钙结合蛋白S100 A4，该蛋白在白色变性区域强烈上调。为了研究白色星形胶质细胞及其特异性蛋白S100 A4在轴突再生中的作用，我们开发了具有强S100 A4表达的白色星形胶质细胞培养物，并在星形胶质细胞顶部培养分离的成年背根神经节（DRG）细胞24小时。我们能够消除S100 A4表达并比较S100 A4沉默和S100 A4表达星形胶质细胞上DRG细胞神经突的生长。此外，我们研究了细胞外S100 A4是否对在表达S100 A4的白色星形胶质细胞上培养的成年DRG细胞的神经突生长有影响。我们的数据表明，白色星形胶质细胞是允许的神经突生长，虽然在白色星形胶质细胞的S100 A4高水平有负面影响，这种增长。细胞外应用S100 A4诱导DRG细胞神经突起在白色星形胶质细胞上广泛生长。这些发现表明，白色物质星形胶质细胞能够支持轴突再生，此外，细胞外S100 A4的管理提供了强大的额外支持轴突再生。(C)2006 Wiley-Liss，Inc.
The central nervous system (CNS) is considered a non-permissive environment for axonal regeneration because of the presence of myelin and associated repulsive molecules. However, neural cells transplanted to the CNS preferably migrate and extend their fibers in white matter areas. We previously showed that white matter astrocytes in vivo express the calcium-binding protein S100A4, which is strongly up-regulated in areas of white matter degeneration. To investigate the role of white matter astrocytes and their specific protein S100A4 in axonal regeneration, we developed white matter astrocyte cultures with strong S100A4 expression and grew dissociated adult dorsal root ganglion (DRG) cells on top of astrocytes for 24 hr. By using small interfering S100A4 RNA, we were able to eliminate S100A4 expression and compare growth of DRG cell neurites on S100A4-silenced and S100A4-expressing astrocytes. in addition, we studied whether extracellular S100A4 has an effect on neurite growth from adult DRG cells cultured on S100A4-expressing white matter astrocytes. Our data show that white matter astrocytes are permissive for neurite growth, although high levels of S100A4 in white matter astrocytes have a negative effect on this growth. Extracellular application of S100A4 induced extensive growth of DRG cell neurites on white matter astrocytes. These findings suggest that white matter astrocytes are able to support axonal regeneration and, furthermore, that administration of extracellular S100A4 provides strong additional support for axonal regeneration. (C) 2006 Wiley-Liss, Inc.