miR-9 inhibits Schwann cell migration by targeting Cthrc1 following sciatic nerve injury
miR-9 inhibits Schwann cell migration by targeting Cthrc1 following sciatic nerve injury
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坐骨神经损伤后 miR-9 通过靶向 Cthrc1 抑制雪旺细胞迁移
DOI：
10.1242/jcs.131672
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发表时间：
2014-03-01
影响因子：
4
通讯作者：
Gu, Xiaosong
中科院分区：
文献类型：
--
作者：
Zhou, Songlin;Gao, Rong;Gu, Xiaosong
microRNA（miRNAs）对雪旺细胞对神经损伤刺激的反应的调节作用尚不清楚。在本研究中，我们注意到8种miRNAs在大鼠坐骨神经切断后不同时间点的表达下调，并发现这8种miRNAs的368个潜在靶点主要参与雪旺细胞的表型调节。在这些miRNAs中，miR-9被鉴定为雪旺细胞迁移的重要功能调节因子，雪旺细胞迁移是雪旺细胞对神经损伤的关键再生反应。在体外，上调miR-9的表达可抑制雪旺细胞迁移，而沉默miR-9可促进雪旺细胞迁移。有趣的是，miR-9通过直接靶向胶原蛋白三螺旋重复序列蛋白1（CTHRC 1）发挥这种调节功能，CTHRC 1反过来又使下游Rac 1 GT3失活。Rac 1抑制剂降低了抗miR-9对雪旺细胞迁移的促进作用。在体内，miR-9的高表达减少了再生神经微环境中的雪旺细胞迁移。总的来说，我们的研究结果证实了miR-9在神经损伤后调节雪旺细胞迁移中的作用，从而为周围神经修复提供了一种新的方法。
The regulative effects of microRNAs (miRNAs) on responses of Schwann cells to a nerve injury stimulus are not yet clear. In this study, we noted that the expression of eight miRNAs was downregulated at different time points following rat sciatic nerve transection, and found that 368 potential targets of these eight miRNAs were mainly involved in phenotypic modulation of Schwann cells. Of these miRNAs, miR-9 was identified as an important functional regulator of Schwann cell migration that was a crucial regenerative response of Schwann cells to nerve injury. In vitro, upregulated expression of miR-9 inhibited Schwann cell migration, whereas silencing of miR-9 promoted Schwann cell migration. Intriguingly, miR-9 exerted this regulative function by directly targeting collagen triple helix repeat containing protein 1 (CTHRC1), which in turn inactivated downstream Rac1 GTPase. Rac1 inhibitor reduced the promotive effects of anti-miR-9 on Schwann cell migration. In vivo, high expression of miR-9 reduced Schwann cell migration within a regenerative nerve microenvironment. Collectively, our results confirmed the role of miR-9 in regulating Schwann cell migration after nerve injury, thus offering a new approach to peripheral nerve repair.