Overexpression of P2X4 receptor in Schwann cells promotes motor and sensory functional recovery and remyelination via BDNF secretion after nerve injury
Overexpression of P2X4 receptor in Schwann cells promotes motor and sensory functional recovery and remyelination via BDNF secretion after nerve injury
复制标题
雪旺细胞中 P2X4 受体的过度表达可通过神经损伤后分泌 BDNF 促进运动和感觉功能恢复和髓鞘再生。
作者：
Su Wen Feng;Wu Fan;Jin Zi Han;Gu Yun;Chen Ying Ting;Fei Ying;Chen Hui;Wang Ya Xian;Xing Ling Yan;Zhao Ya Yu;Yuan Ying;Tang Xin;Chen Gang
P2 X4受体（P2 X4 receptor，P2 X4 R）广泛分布于中枢神经系统，包括神经元、星形胶质细胞和小胶质细胞。越来越多的证据支持P2 X4 R在中枢神经系统中的作用，包括调节细胞兴奋性、突触传递和神经性疼痛。然而，关于P2 X4 R在周围神经系统中的分布和功能的信息很少。本研究发现P2 X4 R主要定位于周围神经系统雪旺细胞的溶酶体中。在培养的雪旺细胞中，TNF-α不仅增强P2 X4 R蛋白的合成，而且还促进P2 X4 R运输到雪旺细胞表面。在雪旺细胞中TNF-α诱导的BDNF分泌是P2 X4 R依赖性的。体内实验表明，神经挤压伤后，损伤神经雪旺细胞中P2 X4 R表达显著上调。此外，通过基因操作在雪旺细胞中过表达P2 X4 R促进运动和感觉功能恢复，并通过神经损伤后BDNF释放加速神经髓鞘再生。我们的研究结果表明，增强P2 X4 R在神经损伤后的雪旺细胞的表达可能是一种有效的方法，以促进再生和髓鞘损伤的神经。
Of the seven P2X receptor subtypes, P2X4 receptor (P2X4R) is widely distributed in the central nervous system, including in neurons, astrocytes, and microglia. Accumulating evidence supports roles for P2X4R in the central nervous system, including regulating cell excitability, synaptic transmission, and neuropathic pain. However, little information is available about the distribution and function of P2X4R in the peripheral nervous system. In this study, we find that P2X4R is mainly localized in the lysosomes of Schwann cells in the peripheral nervous system. In cultured Schwann cells, TNF‐a not only enhances the synthesis of P2X4R protein but also promotes P2X4R trafficking to the surface of Schwann cells. TNF‐a‐induced BDNF secretion in Schwann cells is P2X4R dependent. in vivo experiments reveal that expression of P2X4R in Schwann cells of injured nerves is strikingly upregulated following nerve crush injury. Moreover, overexpression of P2X4R in Schwann cells by genetic manipulation promotes motor and sensory functional recovery and accelerates nerve remyelination via BDNF release following nerve injury. Our results suggest that enhancement of P2X4R expression in Schwann cells after nerve injury may be an effective approach to facilitate the regrowth and remyelination of injured nerves.