RAGE modulates peripheral nerve regeneration via recruitment of both inflammatory and axonal outgrowth pathways
RAGE modulates peripheral nerve regeneration via recruitment of both inflammatory and axonal outgrowth pathways
复制标题
DOI：
10.1096/fj.04-1900com
复制
发表时间：
2004-12-01
期刊：
影响因子：
4.8
通讯作者：
Schmidt, AM
中科院分区：
文献类型：
--
作者：
Rong, LL;Yan, SF;Schmidt, AM
周围神经的轴突切开术刺激了多种细胞类型的事件，这些事件引发了轴突变性和损伤后神经突向远端节段同时生长的有限炎症反应。我们发现RAGE的药物阻断会损害RAGE阻断和急性坐骨神经挤压小鼠的周围神经再生。由于我们的研究表明RAGE在轴突和损伤后浸润的单核吞噬细胞中表达，我们测试了RAGE在这些不同细胞类型中对神经再生的作用。在单核吞噬细胞或周围神经元中表达信号转导缺陷的RAGE转基因小鼠，并对坐骨神经进行单侧挤压损伤。通过运动和感觉传导速度来评估，转基因小鼠的功能和形态恢复比对照小鼠有所下降；还有髓鞘纤维密度。在单核吞噬细胞和周围神经元中表达信号转导缺陷RAGE的双转基因小鼠中，再生甚至进一步受损，这表明RAGE调节的炎症和神经突起生长在神经修复中存在关键的相互作用。这些结果表明，炎症细胞和周围神经元中的RAGE信号在周围神经系统的可塑性中起重要作用。
Axotomy of peripheral nerve stimulates events in multiple cell types that initiate a limited inflammatory response to axonal degeneration and simultaneous outgrowth of neurites into the distal segments after injury. We found that pharmacological blockade of RAGE impaired peripheral nerve regeneration in mice subjected to RAGE blockade and acute crush of the sciatic nerve. As our studies revealed that RAGE was expressed in axons and in infiltrating mononuclear phagocytes upon injury, we tested the role of RAGE in these distinct cell types on nerve regeneration. Transgenic mice expressing signal transduction-deficient RAGE in mononuclear phagocytes or peripheral neurons were generated and subjected to unilateral crush injury to the sciatic nerve. Transgenic mice displayed decreased functional and morphological recovery compared with littermate controls, as assessed by motor and sensory conduction velocities; and myelinated fiber density. In double transgenic mice expressing signal transduction deficient RAGE in both mononuclear phagocytes and peripheral neurons, regeneration was even further impaired, suggesting the critical interplay between RAGE-modulated inflammation and neurite outgrowth in nerve repair. These findings suggest that RAGE signaling in inflammatory cells and peripheral neurons plays an important role in plasticity of the peripheral nervous system.