CXCL12 has therapeutic value in facial nerve injury and promotes Schwann cells autophagy and migration via PI3K-AKT-mTOR signal pathway
CXCL12 has therapeutic value in facial nerve injury and promotes Schwann cells autophagy and migration via PI3K-AKT-mTOR signal pathway
复制标题
CXCL12对面神经损伤具有治疗价值，通过PI3K-AKT-mTOR信号通路促进雪旺细胞自噬和迁移
DOI：
10.1016/j.ijbiomac.2018.10.212
复制
发表时间：
2019-03-01
影响因子：
8.2
通讯作者：
Li, Shiting
中科院分区：
文献类型：
--
作者：
Gao, Dekun;Tang, Tianchi;Li, Shiting
面神经损伤是临床上常见的疾病，伴有受损神经的脱髓鞘。受损神经的髓鞘再生和功能恢复不理想是长期困扰人们的问题。CXCL 12在面神经损伤后的作用仍然未知。我们的实验发现，CXCL 12在面神经损伤早期表达上调，2周后表达下降。进一步研究发现CXCL 12对雪旺细胞增殖、凋亡及细胞周期无影响，但明显促进雪旺细胞迁移。用CXCL 12处理降低了P13 K AKT和mTOR的磷酸化，但增加了自噬标志物LC 3 II/I。分别用3-MA和IGF-1预处理抑制自噬和PI 3 K途径激活，可明显减弱CXCL 12诱导的施万细胞迁移，P13 K途径抑制剂LY 294002可增强这种作用。动物实验也证实CXCL 12能促进面神经功能和髓鞘再生。本研究结果表明，CXCL 12可以促进雪旺细胞的迁移，并可能成为面神经损伤修复的关键分子。(C)2018由Elsevier B. V.出版
Facial nerve injury is a clinically common disease accompanied by demyelination of damaged nerves. The remyelination of damaged nerves and the unsatisfactory function recovery are problems that have been plaguing people for a long time. The role that CXCL12 plays after facial nerve injury remains unknown. Our experiments found that the expression of CXCL12 was up-regulated in the early stage of facial nerve injury and decreased after two weeks. Further research found that CXCL12 had no effect on Schwann cells proliferation, apoptosis and cell cycle, while significantly promoted Schwann cells migration. Treatment with CXCL12 decreased the phosphorylation of P13K AKT and mTOR, but increased autophagy marker LC3II/I. The CXCL12-induced Schwann cells migration was significantly attenuated by inhibition of autophagy and activation of PI3K pathway through pretreatment with 3-MA and IGF-1 respectively, and this effect was enhanced by P13K pathway inhibitor LY294002. Animal experiment also confirmed that CXCL12 could improve facial nerve function and myelin regeneration. The findings of this study indicate that CXCL12 can promote the migration of Schwann cells and potentially become a key molecule in the repair of facial nerve injury. (C) 2018 Published by Elsevier B.V.