Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, 226001, Jiangsu, China.
School of Life Sciences, Nantong University, Nantong, 226001, Jiangsu, China.
Mol Neurobiol. 2022 Feb;59(2):1058-1072. doi: 10.1007/s12035-021-02589-2. Epub 2021 Nov 27.
Schwann cells switch to a repair phenotype following peripheral nerve injury and create a favorable microenvironment to drive nerve repair. Many microRNAs (miRNAs) are differentially expressed in the injured peripheral nerves and play essential roles in regulating Schwann cell behaviors. Here, we examine the temporal expression patterns of miR-29a-3p after peripheral nerve injury and demonstrate significant up-regulation of miR-29a-3p in injured sciatic nerves. Elevated miR-29a-3p inhibits Schwann cell proliferation and migration, while suppressed miR-29a-3p executes reverse effects. In vivo injection of miR-29a-3p agomir to rat sciatic nerves hinders the proliferation and migration of Schwann cells, delays the elongation and myelination of axons, and retards the functional recovery of injured nerves. Mechanistically, miR-29a-3p modulates Schwann cell activities via negatively regulating peripheral myelin protein 22 (PMP22), and PMP22 extensively affects Schwann cell metabolism. Our results disclose the vital role of miR-29a-3p/PMP22 in regulating Schwann cell phenotype following sciatic nerve injury and shed light on the mechanistic basis of peripheral nerve regeneration.
施万细胞在周围神经损伤后转变为修复表型，并创造有利的微环境来促进神经修复。许多 microRNAs（miRNAs）在外周神经损伤中差异表达，并在调节施万细胞行为中发挥重要作用。在这里，我们研究了 miR-29a-3p 在周围神经损伤后的时间表达模式，并证明 miR-29a-3p 在损伤的坐骨神经中显著上调。升高的 miR-29a-3p 抑制施万细胞增殖和迁移，而抑制的 miR-29a-3p 则产生相反的效果。体内注射 miR-29a-3p 激动剂到大鼠坐骨神经中，会阻碍施万细胞的增殖和迁移，延迟轴突的伸长和髓鞘形成，并延迟损伤神经的功能恢复。在机制上，miR-29a-3p 通过负调控外周髓鞘蛋白 22（PMP22）来调节施万细胞的活性，而 PMP22 广泛影响施万细胞的代谢。我们的结果揭示了 miR-29a-3p/PMP22 在调节坐骨神经损伤后施万细胞表型中的重要作用，并阐明了周围神经再生的机制基础。
