Versican is upregulated in CNS injury and is a product of oligodendrocyte lineage cells
Versican is upregulated in CNS injury and is a product of oligodendrocyte lineage cells
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DOI：
10.1523/jneurosci.22-06-02225.2002
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发表时间：
2002-03-15
影响因子：
5.3
通讯作者：
Fawcett, JW
中科院分区：
文献类型：
--
作者：
Asher, RA;Morgenstern, DA;Fawcett, JW
硫酸软骨素蛋白聚糖（CS-PG）的表达增加，以响应中枢神经系统损伤，并限制轴突再生的能力。先前我们已经表明，neurocan是上调的CS-PG之一（Asher等人，2000年）。在这里，我们表明，另一个成员的聚集蛋白聚糖家族，多功能蛋白聚糖，也上调中枢神经系统损伤的反应。标记的冷冻切片7天后，单侧刀病变的大脑皮层显示病变周围的versican免疫反应性明显增加。从受伤和未受伤的组织制备的提取物的蛋白质印迹分析也揭示了相当多的多功能蛋白聚糖在受伤的组织提取物。体外研究表明多功能蛋白聚糖是少突胶质细胞谱系细胞（OLC）的产物。在晚期A2 B5阳性阶段和O 1阳性前少突胶质细胞阶段之间观察到标记。未成熟的，双极A2 B5阳性细胞，也没有分化，髓鞘形成少突胶质细胞被标记。条件培养基中多功能蛋白聚糖的量随着这些细胞的分化而增加。Versican和tenascin-R共定位于OLC中，免疫共沉淀表明两者在少突胶质细胞条件培养基中作为复合物存在。用透明质酸酶处理前少突胶质细胞导致多功能蛋白聚糖的释放，表明其在细胞表面的保留依赖于透明质酸（HA）。在大鼠脑中，大约一半的多功能蛋白聚糖与透明质酸结合。我们还提供了CS-PG在少突胶质细胞轴突生长抑制特性中的作用的证据。由于大量的OLC被募集到CNS病变，这些结果表明OLC衍生的多功能蛋白聚糖有助于受损CNS的不适宜环境。
Chondroitin sulfate proteoglycan (CS-PG) expression is increased in response to CNS injury and limits the capacity for axonal regeneration. Previously we have shown that neurocan is one of the CS-PGs that is upregulated (Asher et al., 2000). Here we show that another member of the aggrecan family, versican, is also upregulated in response to CNS injury. Labeling of frozen sections 7 d after a unilateral knife lesion to the cerebral cortex revealed a clear increase in versican immunoreactivity around the lesion. Western blot analysis of extracts prepared from injured and uninjured tissue also revealed considerably more versican in the injured tissue extract. In vitro studies revealed versican to be a product of oligodendrocyte lineage cells (OLCs). Labeling was seen between the late A2B5-positive stage and the O1-positive pre-oligodendrocyte stage. Neither immature, bipolar A2B5-positive cells, nor differentiated, myelin-forming oligodendrocytes were labeled. The amount of versican in conditioned medium increased as these cells differentiated. Versican and tenascin-R colocalized in OLCs, and coimmunoprecipitation indicated that the two exist as a complex in oligodendrocyte-conditioned medium. Treatment of pre-oligodendrocytes with hyaluronidase led to the release of versican, indicating that its retention at the cell surface is dependent on hyaluronate (HA). In rat brain, approximately half of the versican is bound to hyaluronate. We also provide evidence of a role for CS-PGs in the axon growth-inhibitory properties of oligodendrocytes. Because large numbers of OLCs are recruited to CNS lesions, these results suggest that OLC-derived versican contributes to the inhospitable environment of the injured CNS.