Chondroitin sulfate proteoglycan with neurite-inhibiting activity is up-regulated following peripheral nerve injury
Chondroitin sulfate proteoglycan with neurite-inhibiting activity is up-regulated following peripheral nerve injury
复制标题
DOI：
10.1002/(sici)1097-4695(199801)34:1
复制
发表时间：
1998-01-01
期刊：
影响因子：
--
通讯作者：
Muir, D
中科院分区：
文献类型：
--
作者：
Zuo, J;Hernandez, YJ;Muir, D
许多研究结果支持高度硫酸化蛋白聚糖是抑制性分子的可能性，相对于生长促进信号，在高浓度下，可以调节或引导轴突生长。尽管大多数研究表明硫酸化蛋白聚糖与中枢神经系统再生能力差有关，但抑制性蛋白聚糖也可能在周围神经内轴突的成功再生中发挥重要作用，培养的大鼠神经鞘瘤和施万细胞产生硫酸软骨素蛋白聚糖（CSPG），其结合并抑制层粘连蛋白的促神经突活性[Muir等（1989）J. Cell Biol.109：2353]。在本研究中，我们发现了与从正常成年大鼠坐骨神经中分离的CSPG相关的类似的轴突抑制活性，在神经挤压损伤后，这种抑制活性在损伤远端的再生神经中增加了7倍。这种增加在很大程度上通过体内施用蛋白聚糖合成抑制剂β-D-木糖苷而减弱。在正常成人神经中，CSPG核心蛋白的免疫标记集中在轴突-雪旺细胞单位周围的细长带和朗维尔结内。神经挤压伤后，CSPG和层粘连蛋白的免疫标记在远端神经中变得更强，CSPG在神经内膜和周围神经鞘中增加。在纵行神经切片上培养的胚胎背根神经节神经元沿着雪旺细胞基膜外露面伸出突起，突起长度比经硫酸软骨素酶预处理的正常神经切片增加58%。即使层粘连蛋白水平升高，在基底层损伤的神经，神经炎生长的部分损伤的神经没有显着增加，除非部分预处理与软骨素酶。这些结果表明抑制性CSPG在损伤神经中上调，并在调节轴突再生中起作用。(C)John Wiley & Sons，Inc.
Numerous findings support the possibility that highly sulfated proteoglycans are inhibitory molecules which, at high concentration relative to growth-promoting signals, may regulate or guide axonal growth, Although most studies implicate sulfated proteoglycans in the poor regenerative capacity of the central nervous system, inhibitory proteoglycans also may play an important role in the successful regeneration of axons within peripheral nerve, Cultured rat schwannoma and Schwann cells produce chondroitin sulfate proteoglycan (CSPG) which binds to and inhibits the neurite-promoting activity of laminin [Muir et al. (1989) J. Cell Biol. 109:2353]. In the present study, we found a similar neurite-inhibiting activity associated with CSPG isolated from normal adult rat sciatic nerve, Following nerve crush injury, this inhibitory activity was increased sevenfold in regenerating nerve distal to the injury. This increase was largely attenuated by in vivo administration of the proteoglycan synthesis inhibitor beta-D-xyloside. In normal adult nerve, immunolabeling for CSPG core protein was concentrated in slender bands surrounding axon-Schwann cell units and within nodes of Ranvier. Following nerve crush injury, immunolabeling of CSPG and laminin became more intense in distal nerve and CSPG increased within endoneurium and surrounding nerve sheaths. Embryonic dorsal root ganglionic neurons cultured on longitudinal nerve sections extended neurites along the exposed surfaces of Schwann cell basal lamina, The length of neurites was increased 58% on normal nerve sections pretreated with chondroitinase. Even though laminin levels were elevated in basal lamina of injured nerve, neuritic growth on sections of injured nerve was not significant increased unless sections were pretreated with chondroitinase. These results indicate that inhibitory CSPG is up-regulated in injured nerve and plays a role in regulating axonal regeneration. (C) 1998 John Wiley & Sons, Inc.