1Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang,China.
Department of OrthopedicSurgery,The First Affiliated Hospital of China Medical University, Shenyang,China.
Mol Pain. 2017 Jan-Dec;13:1744806917711612. doi: 10.1177/1744806917711612.
Effective axon regeneration is achieved mainly by precise regulation of gene expression after peripheral nerve injury. MicroRNAs play an important role in controlling axon regeneration owe to its key epigenetic function in regulating gene expression. Here, we reveal that microRNA-9 (miR-9) may be a new suppressor of axon regeneration and FoxP1 is the functional target of miR-9. High level of endogenous miR-9 in sensory neurons inhibited axon regeneration in vitro and in vivo. In addition, the regulatory effect of miR-9 was mediated by changes in FoxP1 levels. Full rescuing effect of axon regeneration was achieved by FoxP1 up-regulation. Most importantly, we showed that miR-9-FoxP1 might be a new signaling pathway to regulate mammalian axon regrowth. Moreover, we provided the first evidence that maintaining a higher level of FoxP1 in sensory neurons by the microRNA is necessary for efficient axon regeneration.
有效的轴突再生主要通过外周神经损伤后基因表达的精确调控来实现。microRNA 通过其在调节基因表达方面的关键表观遗传功能,在控制轴突再生方面发挥着重要作用。在这里,我们揭示了 microRNA-9(miR-9)可能是轴突再生的新抑制剂,FoxP1 是 miR-9 的功能靶标。感觉神经元中内源性 miR-9 水平升高抑制了体外和体内的轴突再生。此外,miR-9 的调节作用是通过 FoxP1 水平的变化介导的。FoxP1 的上调实现了轴突再生的完全挽救效果。最重要的是,我们表明 miR-9-FoxP1 可能是调节哺乳动物轴突再生的新信号通路。此外,我们提供了第一个证据,即通过 microRNA 维持感觉神经元中较高水平的 FoxP1 对于有效的轴突再生是必要的。