Toma J G, Pareek S, Barker P, Mathew T C, Murphy R A, Acheson A, Miller F D
Department of Anatomy and Cell Biology, University of Alberta, Edmonton, Canada.
J Neurosci. 1992 Jul;12(7):2504-15. doi: 10.1523/JNEUROSCI.12-07-02504.1992.
Non-neuronal cells of peripheral nerve respond to axonal injury with a series of cellular changes that facilitate neuronal regeneration. To characterize the potential role of the epidermal growth factor (EGF) family of proteins in this response, we monitored the expression of EGF receptor mRNA and protein in the injured rat sciatic nerve. EGF receptor mRNA is synthesized in both primary cultured fibroblasts and Schwann cells, and Schwann cells express EGF receptor-like immunoreactivity. In situ hybridization and immunocytochemistry revealed that EGF receptor mRNA and protein are expressed in Schwann cells and fibroblasts of the sciatic nerve in vivo, and that receptor levels increase following nerve injury. Thirty-six hours postlesion, EGF receptors were expressed in gradients along the nerve both proximal and distal to the lesion, with the highest levels localized adjacent to the transection site. By 72 hr, receptor levels were maintained in a gradient in the proximal segment, but were uniformly increased throughout the portions of the distal segment that were analyzed. These changes were similar to those observed for low-affinity NGF receptor mRNA and protein, with transection causing increased expression in both Schwann cells and fibroblasts. Northern blots confirmed that primary cultured fibroblasts express low-affinity NGF receptor mRNA. To determine whether spatiotemporal gradients were a general characteristic of the nerve injury response, we monitored expression of the mRNA encoding the major myelin protein P0. Levels of P0 mRNA decreased initially in cells immediately adjacent to the transection site and, by 72 hr, were uniformly decreased throughout the distal segment. These data suggest that members of the EGF family of proteins may play a role in the peripheral nerve response to injury, and demonstrate a generalized gradient of cellular responses that commence at the transection site and progress distally in the nerve in the absence of intact axons.
外周神经的非神经元细胞会通过一系列促进神经元再生的细胞变化来应对轴突损伤。为了阐明表皮生长因子（EGF）蛋白家族在这一反应中的潜在作用，我们监测了损伤大鼠坐骨神经中EGF受体mRNA和蛋白的表达。EGF受体mRNA在原代培养的成纤维细胞和雪旺细胞中均有合成，且雪旺细胞表达EGF受体样免疫反应性。原位杂交和免疫细胞化学显示，EGF受体mRNA和蛋白在体内坐骨神经的雪旺细胞和成纤维细胞中表达，并且受体水平在神经损伤后升高。损伤后36小时，EGF受体在损伤部位近端和远端的神经上呈梯度表达，最高水平位于横断部位附近。到72小时时，受体水平在近端段保持梯度，但在分析的远端段各部分均均匀升高。这些变化与低亲和力NGF受体mRNA和蛋白的变化相似，横断导致雪旺细胞和成纤维细胞中表达均增加。Northern印迹证实原代培养的成纤维细胞表达低亲和力NGF受体mRNA。为了确定时空梯度是否是神经损伤反应的普遍特征，我们监测了编码主要髓磷脂蛋白P0的mRNA的表达。P0 mRNA水平最初在紧邻横断部位的细胞中降低，到72小时时，在整个远端段均均匀降低。这些数据表明，EGF蛋白家族成员可能在周围神经损伤反应中发挥作用，并证明了一种普遍的细胞反应梯度，该梯度始于横断部位，并在没有完整轴突的情况下向神经远端进展。
