Chondroitin 6-sulphate synthesis is up-regulated in injured CNS, induced by injury-related cytokines and enhanced in axon-growth inhibitory glia
Chondroitin 6-sulphate synthesis is up-regulated in injured CNS, induced by injury-related cytokines and enhanced in axon-growth inhibitory glia
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DOI：
10.1111/j.1460-9568.2005.03876.x
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发表时间：
2005-01-01
影响因子：
3.4
通讯作者：
Fawcett, JW
中科院分区：
文献类型：
--
作者：
Properzi, F;Carulli, D;Fawcett, JW
硫酸软骨素蛋白聚糖（CSPG）在损伤后的CNS中上调，并主要通过其糖胺聚糖（CS-GAG）链抑制轴突再生。我们分析了CS-GAG合成酶的mRNA水平，并通过层析和免疫细胞化学测定了CS-GAG二糖组成。软骨素6-磺基转移酶1（C6 ST 1）在皮质损伤周围的大多数胶质细胞类型中上调，其硫酸化产物CS-C也选择性上调。用脑损伤后释放的TGF α和TGF β治疗，促进C6 ST 1的表达和原代星形胶质细胞中6-硫酸化CS-GAG的合成。少突胶质细胞、少突胶质细胞前体和脑膜细胞都抑制轴突再生，并且都表达高水平的CS-GAG，包括高水平的6-硫酸化GAG。在轴突生长抑制性Neu 7星形胶质细胞中，C6 ST 1和6-硫酸化GAG以高水平表达，而在允许性A7星形胶质细胞中，它们是不可检测的。这些结果表明，中枢神经系统损伤后CSPG的上调与CS-GAG上的特定硫酸化模式相关，介导蛋白聚糖对轴突再生的抑制特性。
Chondroitin sulphate proteoglycans (CSPGs) are up-regulated in the CNS after injury and inhibit axon regeneration mainly through their glycosaminoglycan (CS-GAG) chains. We have analysed the mRNA levels of the CS-GAG synthesizing enzymes and measured the CS-GAG disaccharide composition by chromatography and immunocytochemistry. Chondroitin 6-sulfotransferase 1 (C6ST1) is up-regulated in most glial types around cortical injuries, and its sulphated product CS-C is also selectively up-regulated. Treatment with TGFalpha and TGFbeta, which are released after brain injury, promotes the expression of C6ST1 and the synthesis of 6-sulphated CS-GAGs in primary astrocytes. Oligodendrocytes, oligodendrocyte precursors and meningeal cells are all inhibitory to axon regeneration, and all express high levels of CS-GAG, including high levels of 6-sulphated GAG. In axon growth-inhibitory Neu7 astrocytes C6ST1 and 6-sulphated GAGs are expressed at high levels, whereas in permissive A7 astrocytes they are not detectable. These results suggest that the up-regulation of CSPG after CNS injury is associated with a specific sulphation pattern on CS-GAGs, mediating the inhibitory properties of proteoglycans on axonal regeneration.