Yi Sheng, Wang Qi-Hui, Zhao Li-Li, Qin Jing, Wang Ya-Xian, Yu Bin, Zhou Song-Lin
Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China.
Neural Regen Res. 2017 Oct;12(10):1708-1715. doi: 10.4103/1673-5374.217351.
Differential expression of miRNAs occurs in injured proximal nerve stumps and includes miRNAs that are firstly down-regulated and then gradually up-regulated following nerve injury. These miRNAs might be related to a Schwann cell phenotypic switch. miR-30c, as a member of this group, was further investigated in the current study. Sprague-Dawley rats underwent sciatic nerve transection and proximal nerve stumps were collected at 1, 4, 7, 14, 21, and 28 days post injury for analysis. Following sciatic nerve injury, miR-30c was down-regulated, reaching a minimum on day 4, and was then upregulated to normal levels. Schwann cells were isolated from neonatal rat sciatic nerve stumps, then transfected with miR-30c agomir and co-cultured in vitro with dorsal root ganglia. The enhanced expression of miR-30c robustly increased the amount of myelin-associated protein in the co-cultured dorsal root ganglia and Schwann cells. We then modeled sciatic nerve crush injury in vivo in Sprague-Dawley rats and tested the effect of perineural injection of miR-30c agomir on myelin sheath regeneration. Fourteen days after surgery, sciatic nerve stumps were harvested and subjected to immunohistochemistry, western blot analysis, and transmission electron microscopy. The direct injection of miR-30c stimulated the formation of myelin sheath, thus contributing to peripheral nerve regeneration. Overall, our findings indicate that miR-30c can promote Schwann cell myelination following peripheral nerve injury. The functional study of miR-30c will benefit the discovery of new therapeutic targets and the development of new treatment strategies for peripheral nerve regeneration.
微小RNA(miRNA)的差异表达出现在受损的近端神经残端,其中包括一些在神经损伤后先下调然后逐渐上调的miRNA。这些miRNA可能与雪旺细胞表型转换有关。作为该组的一员,miR-30c在本研究中得到了进一步研究。对Sprague-Dawley大鼠进行坐骨神经横断,并在损伤后1、4、7、14、21和28天收集近端神经残端进行分析。坐骨神经损伤后,miR-30c下调,在第4天达到最低水平,然后上调至正常水平。从新生大鼠坐骨神经残端分离雪旺细胞,然后用miR-30c激动剂转染,并与背根神经节进行体外共培养。miR-30c表达的增强显著增加了共培养的背根神经节和雪旺细胞中髓鞘相关蛋白的含量。然后,我们在Sprague-Dawley大鼠体内建立坐骨神经挤压损伤模型,并测试神经周围注射miR-30c激动剂对髓鞘再生的影响。手术后14天,收集坐骨神经残端并进行免疫组织化学、蛋白质印迹分析和透射电子显微镜检查。直接注射miR-30c刺激了髓鞘的形成,从而促进了周围神经再生。总体而言,我们的研究结果表明,miR-30c可以促进周围神经损伤后雪旺细胞的髓鞘形成。miR-30c的功能研究将有助于发现新的治疗靶点,并为周围神经再生开发新的治疗策略。