Abe K, Namikawa K, Honma M, Iwata T, Matsuoka I, Watabe K, Kiyama H
Departments of Anatomy and Psychiatry and Neurology, Asahikawa Medical College, Asahikawa, Japan.
J Neurochem. 2001 Apr;77(2):700-3. doi: 10.1046/j.1471-4159.2001.00286.x.
Ciliary neurotrophic factor (CNTF) can prevent injury-induced motor neuron death. However, it is also evident that expression of CNTF in Schwann cells is suppressed during nerve regeneration. In this report, we have addressed the mechanism underlying the down-regulation of CNTF expression in injured nerves using a mouse Schwann cell line IMS32 and mouse sciatic nerve. In IMS32 cells, activation of the Ras extracellular-signal-regulated kinase (ERK) pathway by adenoviral vector-mediated expression of dominant active MEK1 did not alter a basal level of CNTF expression, whereas inhibition of the Ras-ERK pathway by using adenoviral vectors resulted in a marked increase in CNTF expression. This inverse relation between before and after axotomy was also observed in mouse sciatic nerve. In the axotomized sciatic nerve, the phosphorylated ERK was markedly increased; in contrast, the expression of CNTF was markedly decreased. These findings suggest that an inactive state of ERK is crucial for the CNTF expression in Schwann cells, and that activation of ERK following nerve injury critically influences the expression of CNTF. This might well explain why CNTF is highly expressed in quiescent Schwann cells in the peripheral nervous system, and also why CNTF is not abundant in axotomized nerves or cultured Schwann cells in which the proliferation signal is obviously active.
睫状神经营养因子（CNTF）可预防损伤诱导的运动神经元死亡。然而，神经再生过程中施万细胞中CNTF的表达受到抑制这一点也很明显。在本报告中，我们利用小鼠施万细胞系IMS32和小鼠坐骨神经，探讨了损伤神经中CNTF表达下调的机制。在IMS32细胞中，腺病毒载体介导的显性活性MEK1表达激活Ras细胞外信号调节激酶（ERK）途径，并未改变CNTF的基础表达水平，而使用腺病毒载体抑制Ras-ERK途径则导致CNTF表达显著增加。在小鼠坐骨神经中也观察到了轴突切断前后的这种相反关系。在切断轴突的坐骨神经中，磷酸化的ERK明显增加；相反，CNTF的表达明显减少。这些发现表明，ERK的非活性状态对施万细胞中CNTF的表达至关重要，并且神经损伤后ERK的激活严重影响CNTF的表达。这很可能解释了为什么CNTF在周围神经系统静止的施万细胞中高表达，以及为什么在轴突切断的神经或增殖信号明显活跃的培养施万细胞中CNTF不丰富。
