Zuo J, Hernandez Y J, Muir D
Department of Pediatrics, University of Florida College of Medicine, Gainesville 32610-0296, USA.
J Neurobiol. 1998 Jan;34(1):41-54.
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.
众多研究结果支持这样一种可能性，即高度硫酸化的蛋白聚糖是抑制性分子，相对于促进生长的信号而言，在高浓度时可能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，但抑制性蛋白聚糖在外周神经轴突的成功再生中也可能起重要作用。培养的大鼠施万细胞瘤和施万细胞产生硫酸软骨素蛋白聚糖（CSPG），它能结合并抑制层粘连蛋白的神经突促进活性[缪尔等人（1989年）《细胞生物学杂志》109:2353]。在本研究中，我们发现从正常成年大鼠坐骨神经中分离出的CSPG具有类似的神经突抑制活性。神经挤压伤后，损伤远端再生神经中的这种抑制活性增加了七倍。通过体内给予蛋白聚糖合成抑制剂β-D-木糖苷，这种增加在很大程度上得到了减弱。在正常成年神经中，CSPG核心蛋白的免疫标记集中在围绕轴突-施万细胞单元的细带以及郎飞结内。神经挤压伤后，远端神经中CSPG和层粘连蛋白的免疫标记变得更强，神经内膜和周围神经鞘内的CSPG增加。在纵向神经切片上培养的胚胎背根神经节神经元沿着施万细胞基膜的暴露表面延伸神经突。在用软骨素酶预处理的正常神经切片上，神经突的长度增加了58%。尽管损伤神经基膜中层粘连蛋白水平升高，但除非用软骨素酶预处理切片，否则损伤神经切片上的神经突生长并没有显著增加。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。
