SGK1 in Schwann cells is a potential molecular switch involved in axonal and glial regeneration during peripheral nerve injury
SGK1 in Schwann cells is a potential molecular switch involved in axonal and glial regeneration during peripheral nerve injury
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雪旺细胞中的 SGK1 是参与周围神经损伤期间轴突和神经胶质再生的潜在分子开关
DOI：
10.1016/j.bbrc.2022.03.123
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发表时间：
2022
影响因子：
3.1
通讯作者：
Mase Mitsuhito
中科院分区：
文献类型：
--
作者：
Okura Atsuhiko;Inoue Koichi;Sakuma Eisuke;Takase Hiroshi;Ueki Takatoshi;Mase Mitsuhito
雪旺细胞在外周髓鞘形成中起重要作用，这些细胞的功能障碍导致轴突损伤。周围神经损伤后雪旺细胞变性。未成熟的雪旺细胞增殖、分化，并在恢复期间支持轴突再生和延伸。在髓鞘形成过程中有许多细胞内信号参与。虽然雪旺细胞中的血清和糖皮质激素诱导激酶（SGK1）被认为参与了髓鞘形成的发育，但其在周围神经损伤和修复过程中的意义仍然未知。在这项研究中，我们研究了周围神经修复过程中SGK 1的动态变化以及SGK在这一过程中的潜在作用。在小鼠麻醉下，首先在右侧坐骨神经中产生轴突挤压损伤，其表现出明显的瘫痪和随后的受损后肢恢复。免疫组化分析显示，外观的胶质细胞酸性蛋白（GFAP）阳性的未成熟的雪旺细胞周围受损的神经，和SGK 1存在于这些细胞。接下来，我们使用S16细胞，一种雪旺细胞系，来探索SGK1对雪旺细胞的影响。SGK抑制剂gsk650394的施用降低了细胞增殖并增加了细胞大小。SGK抑制没有引起细胞损伤，这表明它抑制增殖并扩大雪旺细胞而不引起细胞死亡。此外，定量PCR和免疫印迹显示，SGK抑制上调BDNF，MBP和Krox20的基因表达，这是髓鞘形成和神经再生的促进因子，并下调Sox10。总之，这些发现表明，在雪旺细胞中SGK1失活将细胞命运从增殖转向分化。
Schwann cells play an important role in peripheral myelination, and dysfunction of these cells leads to axonal damage. Schwann cells degenerate following peripheral nerve injury. Immature Schwann cells proliferate, differentiate, and support axonal regeneration and extension during recovery. There are a lot of intracellular signals involved in the myelination process. Although serum- and glucocorticoid-inducible kinase (SGK1) in Schwann cells is supposedly involved in developmental myelination, its significance during peripheral nerve injury and repair remains unknown. In this study, we examined the dynamics of SGK1 during peripheral nerve repair and the potential role of SGK in the process. Axonal crush injury was first generated in the right sciatic nerve under anesthesia in mice, which exhibited apparent paralysis and subsequent recovery of the injured hindlimbs. Immunohistochemical analysis revealed the appearance of glial fibrillary acidic protein (GFAP)-positive immature Schwann cells around injured nerves, and SGK1 was present in these cells. Next, we employed S16 cells, a Schwann cell line, to explore the impact of SGK1 on Schwann cells. Administration of the SGK inhibitor gsk650394 decreased cell proliferation and increased cell size. SGK inhibition did not cause cellular injury, suggesting that it suppresses proliferation and enlarges Schwann cells without causing cell death. Furthermore, quantitative PCR and immunoblotting revealed that SGK inhibition upregulated the gene expression of BDNF, MBP, and Krox20, which are facilitating factors for myelination and neural regeneration, and downregulated that of Sox10. Taken together, these findings indicate that SGK1 inactivation in Schwann cells diverts cell fate from proliferation to differentiation.