Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, China.
Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, PR China.
Exp Cell Res. 2022 Mar 15;412(2):113019. doi: 10.1016/j.yexcr.2022.113019. Epub 2022 Jan 24.
Schwann cells (SCs) play a critical role in peripheral nerve (PN) regeneration because of their ability to proliferate, migrate, and provide trophic support for axon regeneration after PN injury. However, the underlying mechanism is still partially understood. Semaphorin3E (Sema3E), a member of the Sema3s family, is a secreted molecular known as a repelling cue in axon guidance and inhibitor of developmental and postischemic angiogenesis. In this study, we examined the expression of Sema3E in sciatic nerves and SCs and explored the effects of Sema3E on SCs proliferation and migration. Immunofluorescence and ELISA analyses illustrated the expression of Sema3E in SCs of Sciatic nerves and the secretion of Sema3E by cultured SCs, respectively. Exogenous Sema3E promoted SC proliferation and migration while knockdown of the endogenous Sema3E by siRNA transfection attenuated proliferation and migration of SCs. Furthermore, blocking the receptor Neuropilin 1 (Nrp1), PlexinD1 and Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) by neutralizing antibody or inhibitor suppressed the promoting effects of Sema3E on SCs. This study indicated that Sema3E promoted SC proliferation and migration and the involvement of receptor PlexinD1, Nrp1, and VEGFR2 in these processes. This study extended our understanding of the mechanism that modulated SC phenotype during nerve injury and provided a potential target for promoting PN regeneration.
施万细胞 (SCs) 在周围神经 (PN) 再生中发挥着关键作用，因为它们能够在 PN 损伤后增殖、迁移并为轴突再生提供营养支持。然而，其潜在机制仍部分未知。Semaphorin3E (Sema3E) 是 Sema3s 家族的一员，是一种分泌型分子，在轴突导向中作为排斥信号，在发育和缺血后血管生成中作为抑制剂。在本研究中，我们研究了 Sema3E 在坐骨神经和 SCs 中的表达，并探索了 Sema3E 对 SCs 增殖和迁移的影响。免疫荧光和 ELISA 分析分别说明了 Sema3E 在坐骨神经 SCs 中的表达和培养的 SCs 中 Sema3E 的分泌。外源性 Sema3E 促进了 SC 的增殖和迁移，而 siRNA 转染下调内源性 Sema3E 则减弱了 SC 的增殖和迁移。此外，通过中和抗体或抑制剂阻断受体 Neuropilin 1 (Nrp1)、PlexinD1 和血管内皮生长因子受体 2 (VEGFR2) 抑制了 Sema3E 对 SCs 的促进作用。本研究表明 Sema3E 促进了 SC 的增殖和迁移，并且受体 PlexinD1、Nrp1 和 VEGFR2 参与了这些过程。本研究扩展了我们对神经损伤过程中调节 SC 表型的机制的理解，并为促进 PN 再生提供了一个潜在的靶点。
