Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Co-Innovation Center of Neuroregeneration, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong University, Nantong, 226001, China.
Department of General Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, PR China.
Exp Cell Res. 2023 Mar 15;424(2):113506. doi: 10.1016/j.yexcr.2023.113506. Epub 2023 Feb 9.
After peripheral nerve injury, motor and sensory axons can regenerate, but the inaccurate reinnervation of the target leads to poor functional recovery. Schwann cells (SCs) express sensory and motor phenotypes associated with selective regeneration. Semaphorin 3A (Sema3A) is an axonal chemorepellent that plays an essential role in axon growth. SCs can secret Sema3A, and Sema3A presents a different expression pattern at the proximal and distal ends of injured sensory and motor nerves. Hence, in our study, the protein expression and secretion of Sema3A in sensory and motor SCs and the expression of its receptor Neuropilin-1 (Nrp1) in dorsal root ganglia (DRG) sensory neurons (SNs) and spinal cord motor neurons (MNs) were detected by Western blot and ELISA. The effect of Sema3A at different concentrations on neurite growth of sensory and motor neurons was observed by immunostaining. Also, by blocking the Nrp1 receptor on neurons, the effect of Sema3A on neurite growth was observed. Finally, we observed the neurite growth of sensory and motor neurons cocultured with Sema3A siRNA transfected SCs by immunostaining. The results suggested that the expression and secretion of Sema3A in sensory SCs are more significant than that in motor SCs, and the expression of its receptor Nrp1 in SNs is higher than in MNs. Sema3A could inhibit the neurite growth of sensory and motor neurons via Nrp1, and Sema3A has a more substantial effect on the neurite growth of SNs. These data provide evidence that SC-secreted Sema3A might play a role in selective regeneration by a preferential effect on SNs.
外周神经损伤后，运动和感觉轴突可以再生，但靶神经的神经再支配不准确导致功能恢复不良。雪旺细胞（SCs）表达与选择性再生相关的感觉和运动表型。神经调节蛋白 3A（Sema3A）是一种轴突化学排斥物，在轴突生长中起重要作用。SCs 可以分泌 Sema3A，并且 Sema3A 在损伤的感觉和运动神经的近端和远端呈现出不同的表达模式。因此，在我们的研究中，通过 Western blot 和 ELISA 检测了感觉和运动 SC 中 Sema3A 的蛋白表达和分泌以及感觉神经节（DRG）感觉神经元（SNs）和脊髓运动神经元（MNs）中其受体 Neuropilin-1（Nrp1）的表达。通过免疫染色观察不同浓度的 Sema3A 对感觉和运动神经元轴突生长的影响。此外，通过阻断神经元上的 Nrp1 受体，观察 Sema3A 对轴突生长的影响。最后，通过免疫染色观察与转染 Sema3A siRNA 的 SC 共培养的感觉和运动神经元的轴突生长。结果表明，感觉 SC 中 Sema3A 的表达和分泌比运动 SC 更显著，其受体 Nrp1 在 SNs 中的表达高于 MNs。Sema3A 可以通过 Nrp1 抑制感觉和运动神经元的轴突生长，并且 Sema3A 对 SNs 的轴突生长有更显著的影响。这些数据提供了证据，表明 SC 分泌的 Sema3A 可能通过对 SNs 的优先影响在选择性再生中发挥作用。
