Schwann Cell Migration is Integrin-Dependent and Inhibited by Astrocyte-Produced Aggrecan
Schwann Cell Migration is Integrin-Dependent and Inhibited by Astrocyte-Produced Aggrecan
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DOI：
10.1002/glia.20970
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发表时间：
2010-05-01
期刊：
影响因子：
6.2
通讯作者：
Fawcett, James W.
中科院分区：
文献类型：
--
作者：
Afshari, Fardad T.;Kwok, Jessica C.;Fawcett, James W.
雪旺细胞移植在脊髓创伤中具有相当大的前景，可以桥接损伤部位和脱髓鞘条件下的再髓鞘形成。它们通过分泌生长因子和提供允许的表面和基质分子来支持轴突再生和发芽，同时保护轴突免受中枢神经系统的抑制环境的影响。然而，移植后雪旺细胞表现出有限的迁移能力，它们不能与宿主星形胶质细胞混合。这反过来导致雪旺细胞移植物与宿主组织星形胶质细胞之间形成一个尖锐的边界和突变，从而阻止再生轴突从移植物中退出。本研究的目的是确定星形胶质细胞参与限制雪旺细胞迁移的抑制因子。通过体外细胞迁移实验，我们发现星形胶质细胞产生的聚集蛋白参与了星形胶质细胞单层上雪旺细胞运动的抑制。在星形胶质细胞中使用RNAi敲除这种蛋白多糖或在聚集蛋白上消化糖多糖链可以改善雪旺细胞的迁移。我们进一步表明，聚集蛋白通过破坏雪旺细胞中整合素的功能来介导其作用，并且可以通过激活雪旺细胞整合素来克服聚集蛋白的抑制作用。(C) 2010 Wiley-Liss, Inc。
Schwann cells transplantation has considerable promise in spinal cord trauma to bridge the site of injury and for remyelination in demyelinating conditions. They support axonal regeneration and sprouting by secreting growth factors and providing a permissive surface and matrix molecules while shielding axons from the inhibitory environment of the central nervous system. However, following transplantation Schwann cells show limited migratory ability and they are unable to intermingle with the host astrocytes. This in turn leads to formation of a sharp boundary and an abrupt transition between the Schwann cell graft and the host tissue astrocytes, therefore preventing regenerating axons from exiting the graft. The objective of this study was to identify inhibitory elements on astrocytes involved in restricting Schwann cell migration. Using in vitro assays of cell migration, we show that aggrecan produced by astrocytes is involved in the inhibition of Schwann cell motility on astrocytic monolayers. Knockdown of this proteoglycan in astrocytes using RNAi or digestion of glycosaminglycan chains on aggrecan improves Schwann cell migration. We further show aggrecan mediates its effect by disruption of integrin function in Schwann cells, and that the inhibitory effects of aggrecan can overcome by activation of Schwann cell integrins. (C) 2010 Wiley-Liss, Inc.