Possible involvement of increase in spinal fibronectin a following peripheral nerve injury in upregulation of microglial P2X4, a key molecule for mechanical allodynia
Possible involvement of increase in spinal fibronectin a following peripheral nerve injury in upregulation of microglial P2X4, a key molecule for mechanical allodynia
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作者：
Nasu-Tada, K;Koizumi, S;Inoue, K
我们最近证明，脊髓小胶质细胞中的P2X(4)受体（atp门控阳离子通道）是介导周围神经损伤引起的机械性异常痛的关键分子。尽管周围神经损伤后小胶质细胞P2X(4)受体表达增加，但其上调的分子机制仍不清楚。纤维连接蛋白是细胞外基质分子的一员，在中枢神经系统损伤和疾病的反应中积极产生。在这里，我们描述了纤维连接蛋白对小胶质细胞P2X(4)受体表达的影响以及周围神经损伤后纤维连接蛋白的上调。与在对照培养皿中培养的小胶质细胞相比，在纤维连接蛋白包被培养皿中培养的小胶质细胞在mRNA和蛋白水平上的P2X(4)受体表达均显著增加。纤连蛋白也增强了P2X(4)受体介导的小胶质细胞Ca2+反应。此外，脊髓损伤大鼠脊髓的Western blot检查显示，同侧纤维连接蛋白上调。有趣的是，鞘内注射atp刺激的小胶质细胞到大鼠腰椎脊髓显示，在纤维连接蛋白包被的培养皿中培养的小胶质细胞比在对照培养皿中培养的小胶质细胞更有效地诱导异位性疼痛。综上所述，我们的研究结果表明，脊髓纤维连接蛋白在周围神经损伤后升高，可能参与了小胶质细胞P2X(4)受体的上调，从而导致神经性疼痛的发生。(c) 2006年威利利斯。
We have recently demonstrated that the P2X(4) receptor, an ATP-gated cation channel, in spinal microglia is a key molecule that mediates the mechanical allodynia induced by peripheral nerve injury. Although microglial P2X(4) receptor expression is increased after peripheral nerve injury, the molecular mechanism(s) underlying its upregulation remains largely unknown. Fibronectin is a member of the extracellular matrix molecules and is actively produced in response to injury and diseases in the CNS. Here, we describe the influence of fibronectin on P2X(4) receptor expression in microglia and the upregulation of fibronectin after peripheral nerve injury. Microglia that were cultured on fibronectin-coated dishes showed a marked increase in P2X(4) receptor expression, both at the mRNA and protein levels, as compared to those cultured on control dishes. Fibronectin also enhanced the microglial Ca2+ responses mediated by P2X(4) receptors. Moreover, Western blot examination of the spinal cord from a rat with spinal nerve injury indicated that fibronectin was upregulated on the ipsilateral side. Interestingly, intrathecal injection of ATP-stimulated microglia to the rat lumber spinal cord revealed that microglia cultured on fibronectin-coated dishes was more effective in the induction of allodynia than microglia cultured on control dishes. Taken together, our results suggest that spinal fibronectin is elevated after the peripheral nerve injury and it may be involved in the upregulation of the P2X(4) receptor in microglia, which leads to the induction of neuropathic pain. (c) 2006 Wiley-Liss.