Liu Xiangyu, Yu Xueyuan, He Youcheng, Wang Lu
Department of Aesthetic Plastic & Craniofacial Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
J Cell Physiol. 2019 Sep;234(9):16357-16366. doi: 10.1002/jcp.28302. Epub 2019 Feb 12.
The proliferation and migration of Schwann cells contribute to axonal outgrowth and functional recovery after peripheral nerve injury. Studies have found that long noncoding RNAs (lncRNAs) were abnormally expressed after peripheral nerve injury and they played vital roles in peripheral nerve regeneration. LncRNA nuclear enriched abundant transcript 1 (NEAT1) was increased in the cerebral cortex surrounding the injury site of mice after traumatic brain injury, and it promoted the functional recovery in mice. However, its role and mechanism in peripheral nerve injury remain unknown. The expression of NEAT1, miR-34a, and Special AT-rich sequence-binding protein-1 (Satb1) was detected in the sciatic nerve of mice after sciatic nerve crush at 0, 1, 4 and 7 days. The effects of NEAT1 on the proliferation and migration of Schwann cells were detected by 5-Ethynyl-20-deoxyuridine (Edu) and transwell by gain- and loss-of-functions. The mechanism was focused on the miR-34a/Satb1 pathway. In addition, the effect of NEAT1 in Schwann cells on axon outgrowth of dorsal root ganglion neurons was further investigated. We found that the NEAT1 and Satb1 expression was increased, whereas miR-34a was reduced, in injured sciatic nerve at different time points. Overexpression of NEAT1 promoted, whereas knockdown of NEAT1 suppressed the proliferation and migration of Schwann cells. NEAT1 functioned as a competing endogenous RNA to regulate the Satb1 expression via sponging miR-34a. NEAT1 enhanced the axon outgrowth of dorsal root ganglion neurons via regulating the miR-34a and Satb1 expression. In conclusion, NEAT1 promotes the proliferation and migration of Schwann cell via miR-34a/Satb1, which may provide a new approach to peripheral nerve regeneration.
雪旺细胞的增殖和迁移有助于周围神经损伤后轴突的生长和功能恢复。研究发现，长链非编码RNA（lncRNAs）在周围神经损伤后表达异常，且在周围神经再生中发挥着重要作用。长链非编码RNA核富集丰富转录本1（NEAT1）在创伤性脑损伤小鼠损伤部位周围的大脑皮层中表达增加，并促进了小鼠的功能恢复。然而，其在周围神经损伤中的作用和机制尚不清楚。在坐骨神经挤压后0、1、4和7天，检测小鼠坐骨神经中NEAT1、miR-34a和富含特殊AT序列结合蛋白1（Satb1）的表达。通过功能获得和功能缺失实验，利用5-乙炔基-2'-脱氧尿苷（Edu）和Transwell检测NEAT1对雪旺细胞增殖和迁移的影响。机制研究聚焦于miR-34a/Satb1通路。此外，进一步研究了NEAT1在雪旺细胞中对背根神经节神经元轴突生长的影响。我们发现，在不同时间点，损伤的坐骨神经中NEAT1和Satb1表达增加，而miR-34a表达降低。NEAT1的过表达促进了雪旺细胞的增殖和迁移，而NEAT1的敲低则抑制了雪旺细胞的增殖和迁移。NEAT1作为一种竞争性内源性RNA，通过结合miR-34a来调节Satb1的表达。NEAT1通过调节miR-34a和Satb1的表达增强了背根神经节神经元的轴突生长。总之，NEAT1通过miR-34a/Satb1促进雪旺细胞的增殖和迁移，这可能为周围神经再生提供一种新方法。
