Unfolded protein response-induced expression of long noncoding RNA Ngrl1 supports peripheral axon regeneration by activating the PI3K-Akt pathway
Unfolded protein response-induced expression of long noncoding RNA Ngrl1 supports peripheral axon regeneration by activating the PI3K-Akt pathway
复制标题
未折叠蛋白反应诱导长非编码 RNA Ngrl1 的表达通过激活 PI3K-Akt 通路支持外周轴突再生
DOI：
10.1016/j.expneurol.2022.114025
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发表时间：
2022-02
影响因子：
5.3
通讯作者：
Jianwei Zhu
中科院分区：
文献类型：
--
作者：
Dong Wang;Tiemei Zheng;Xiangyu Ge;Jiacheng Xu;Lingling Feng;Chenxiao Jiang;Jincheng Tao;Yuanyuan Chen;Xiaohong Liu;Bin Yu;Songlin Zhou;Jianwei Zhu
In mammals, long noncoding RNA (LncRNA) contributes to neuronal development and injury repair mediated by the spatiotemporal regulation of gene expression. However, the pivotal role of lncRNA in intrinsic axon regeneration control following a nerve injury remains unknown. In this article, we report a neurite growth-related lncRNA termed Ngrl1, which supported peripheral axon regeneration post sciatic nerve crush (SNC). A rapid increase in Ngrl1 expression was detected following SNC, and knockdown of Ngrl1 impaired axon regeneration bothin vitroandin vivo. The unfolded protein response (i.e., the upstream modulator of Ngrl1 expression) improved the impairment of neurite growth induced by Ngrl1 inhibition in matured dorsal root ganglion neurons. Meanwhile, interference with Ngrl1 impacts the PI3K-Akt pathway, leading to a marked decrease in Akt phosphorylation. Furthermore, the activation of Akt by insulin-like growth factor 1 (IGF-1) or SC79 reversed the reduction of axon regeneration in dorsal root ganglion neuron following inhibition of Ngrl1. In conclusion, unfolded protein response-induced Ngrl1 expression supports the intrinsic control of peripheral axon regeneration by modulating the activation of the PI3K-Akt pathway following SNC.
