Laboratory for Neuroregeneration, Netherlands Institute for Neuroscience, An Institute of the Royal Academy of Arts and Sciences, Amsterdam, The Netherlands.
Department of Neurosurgery, Leiden University Medical Center, Leiden, The Netherlands.
PLoS One. 2021 Apr 13;16(4):e0249748. doi: 10.1371/journal.pone.0249748. eCollection 2021.
A human neuroma-in continuity (NIC), formed following a peripheral nerve lesion, impedes functional recovery. The molecular mechanisms that underlie the formation of a NIC are poorly understood. Here we show that the expression of multiple genes of the Wnt family, including Wnt5a, is changed in NIC tissue from patients that underwent reconstructive surgery. The role of Wnt ligands in NIC pathology and nerve regeneration is of interest because Wnt ligands are implicated in tissue regeneration, fibrosis, axon repulsion and guidance. The observations in NIC prompted us to investigate the expression of Wnt ligands in the injured rat sciatic nerve and in the dorsal root ganglia (DRG). In the injured nerve, four gene clusters were identified with temporal expression profiles corresponding to particular phases of the regeneration process. In the DRG up- and down regulation of certain Wnt receptors suggests that nerve injury has an impact on the responsiveness of injured sensory neurons to Wnt ligands in the nerve. Immunohistochemistry showed that Schwann cells in the NIC and in the injured nerve are the source of Wnt5a, whereas the Wnt5a receptor Ryk is expressed by axons traversing the NIC. Taken together, these observations suggest a central role for Wnt signalling in peripheral nerve regeneration.
人神经瘤-连续性（NIC）是在外周神经损伤后形成的，它阻碍了功能的恢复。目前对于形成 NIC 的分子机制还了解甚少。本文作者发现，在接受重建手术的患者的 NIC 组织中，多个 Wnt 家族基因（包括 Wnt5a）的表达发生了改变。Wnt 配体在 NIC 病理和神经再生中的作用引起了人们的关注，因为 Wnt 配体与组织再生、纤维化、轴突排斥和导向有关。在 NIC 中的观察结果促使作者研究了 Wnt 配体在损伤大鼠坐骨神经和背根神经节（DRG）中的表达。在损伤的神经中，确定了四个基因簇，它们的时间表达谱与再生过程的特定阶段相对应。在 DRG 中，某些 Wnt 受体的上调和下调表明神经损伤会影响受伤感觉神经元对神经中 Wnt 配体的反应性。免疫组织化学显示，NIC 和损伤神经中的施万细胞是 Wnt5a 的来源，而穿过 NIC 的轴突表达 Wnt5a 受体 Ryk。综上所述，这些观察结果表明 Wnt 信号在周围神经再生中起着核心作用。
