Overexpression of Rictor in the injured spinal cord promotes functional recovery in a rat model of spinal cord injury
Overexpression of Rictor in the injured spinal cord promotes functional recovery in a rat model of spinal cord injury
复制标题
Rictor 在受损脊髓中的过度表达促进脊髓损伤大鼠模型的功能恢复
DOI：
10.1096/fj.201903171r
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发表时间：
2020-03-31
期刊：
影响因子：
4.8
通讯作者：
Wei, Fuxin
中科院分区：
文献类型：
--
作者：
Chen, Ningning;Zhou, Pengxiang;Wei, Fuxin
Rictor是一种直接激活哺乳动物雷帕霉素靶蛋白（mTOR）活性的重要成分，其有助于成年感觉神经元损伤后的内在轴突生长能力。然而，它的作用是否也适用于脊髓损伤（SCI）后的再生仍然未知。在这项研究中，大鼠在T9 - 10水平脊髓挫伤以建立SCI模型，随后通过脊髓内注射Rictor过表达慢病毒载体以局部上调受损脊髓中的Rictor表达进行治疗。此后，我们研究了Rictor过表达在SCI大鼠损伤脊髓中的治疗作用。与对照慢病毒载体注射治疗组相比，Rictor过表达不仅显著减弱了SCI后的急性炎症反应和细胞死亡，而且显著增加了病变周围巨噬细胞从M1表型向M2表型的转变。此外，Rictor过表达显著增加损伤中心的神经发生，随后促进SCI大鼠的组织修复和功能恢复。有趣的是，Rictor过表达对SCI有益影响的机制可能与Rictor过表达在抗炎反应中发挥作用并驱动巨噬细胞向M2表型极化有关，这有利于常驻神经元和少突胶质细胞的生存。我们的研究结果表明，Rictor是一个有效的目标，影响抑制脊髓再生的分子的产生。总之，局部Rictor过度表达代表了一个有前途的潜在战略，为SCI的修复。
Rictor is an essential component that directly activates the mammalian target of rapamycin (mTOR) activity, which contributes to the intrinsic axon growth capacity of adult sensory neurons after injury. However, whether its action also applies to regeneration after spinal cord injury (SCI) remains unknown. In this study, rats were given spinal cord contusion at the T9‐10 level to establish the SCI model and were subsequently treated with intraspinal cord injection of a Rictor overexpression lentiviral vector to locally upregulate the Rictor expression in the injured spinal cord. Thereafter, we investigated the therapeutic effects of Rictor overexpression in the injured spinal cords of SCI rats. Rictor overexpression not only significantly attenuated the acute inflammatory response and cell death after SCI but also markedly increased the shift in macrophages around the lesion from the M1 to M2 phenotype compared to those of the control lentiviral vector injection‐treated group. Furthermore, Rictor overexpression dramatically increased neurogenesis in the lesion epicenter, subsequently promoting the tissue repair and functional recovery in SCI rats. Interestingly, the mechanism underlying the beneficial effects of Rictor overexpression on SCI may be associated with the Rictor overexpression playing a role in the anti‐inflammatory response and driving macrophage polarization toward the M2 phenotype, which benefits resident neuronal and oligodendrocyte survival. Our findings demonstrate that Rictor is an effective target that affects the generation of molecules that inhibit spinal cord regeneration. In conclusion, localized Rictor overexpression represents a promising potential strategy for the repair of SCI.