Nogo-A promotes inflammatory heat hyperalgesia by maintaining TRPV-1 function in the rat dorsal root ganglion neuron
Nogo-A promotes inflammatory heat hyperalgesia by maintaining TRPV-1 function in the rat dorsal root ganglion neuron
复制标题
Nogo-A 通过维持大鼠背根神经节神经元中的 TRPV1 功能促进炎症热痛觉过敏
DOI：
10.1096/fj.201800382rr
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发表时间：
2019-01-01
期刊：
影响因子：
4.8
通讯作者：
Wang, Jun
中科院分区：
文献类型：
--
作者：
Hu, Fang;Liu, Huai-Cun;Wang, Jun
Nogo-A是少突胶质细胞轴突再生的关键抑制分子。然而，人们对其在成年神经元中的作用知之甚少。在这项研究中，我们发现Nogo-A在调节背根神经节（DRG）神经元的炎症性疼痛方面具有重要功能。成年大鼠后爪完全弗氏佐剂（CFA）炎症后，DRG神经元Nogo-A表达显著增加。用Nogo-66受体拮抗剂肽、Nogo-A阻断抗体、Nogo-A短发夹RNA或Nogo-A基因敲除破坏Nogo-A信号可减轻cfa诱导的炎症性热痛觉过敏。此外，Nogo-A信号的破坏抑制了DRG神经元中瞬时受体电位香草蛋白亚家族成员(TRPV)-1通道的功能和表达，该通道是炎症过程中有害热量的内源性换能器。这些影响伴随着LIM结构域激酶(LIMK)/cofilin磷酸化和肌动蛋白聚合的减少。Latrunculin A直接作用对肌动蛋白丝结构的类似破坏降低了CFA引起的TRPV-1活性和TRPV-1蛋白上调。我们得出结论，Nogo-A在炎症性热痛觉过敏的发展中起着重要作用，部分是通过激活LIMK/cofilin通路来维持TRPV-1的功能，该通路调节肌动蛋白丝动力学。这些发现支持在疼痛管理中调节Nogo-A信号的治疗潜力。胡峰，刘洪成。，苏，D.-Q。陈，H.-J。，陈，s - o。Nogo-A通过维持大鼠背根神经节神经元TRPV-1的功能促进炎症性热痛觉过敏。
Nogo-A is a key inhibitory molecule of axon regeneration in oligodendrocytes. However, little is known about its role in adult neurons. In this study, we showed an important function of Nogo-A on regulation of inflammatory pain in dorsal root ganglion (DRG) neurons. In adult rats with complete Freund's adjuvant (CFA) hind paw inflammation, DRG neurons showed a significant increase in Nogo-A expression. Disruption of Nogo-A signaling with Nogo-66 receptor antagonist peptide, Nogo-A blocking antibody, Nogo-A short hairpin RNA, or Nogo-A gene knockout attenuated CFA-induced inflammatory heat hyperalgesia. Moreover, disruption of Nogo-A signaling suppressed the function and expression in DRG neurons of the transient receptor potential vanilloid subfamily member (TRPV)-1 channel, which is known to be the endogenous transducer of noxious heat during inflammation. These effects were accompanied with a reduction in LIM domain kinase (LIMK)/cofilin phosphorylation and actin polymerization. Similar disruption of actin filament architecture by direct action of Latrunculin A reduced the TRPV-1 activity and up-regulation of TRPV-1 protein caused by CFA. We conclude that Nogo-A plays an essential role in the development of inflammatory heat hyperalgesia, partly through maintaining TRPV-1 function via activation of the LIMK/cofilin pathway, which regulates actin filament dynamics. These findings support a therapeutic potential of modulating Nogo-A signaling in pain management.Hu, F., Liu, H.-C., Su, D.-Q., Chen, H.-J., Chan, S.-O., Wang, Y., Wang, J. Nogo-A promotes inflammatory heat hyperalgesia by maintaining TRPV-1 function in the rat dorsal root ganglion neuron.