Qi Zhi-Ping, Wang Guo-Xiang, Xia Peng, Hou Ting-Ting, Zhou Hong-Li, Wang Tie-Jun, Yang Xiao-Yu
Department of Orthopedics, the Second Hospital of Jilin University, Changchun, Jilin Province, China.
Department of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, China.
Neural Regen Res. 2016 Feb;11(2):332-7. doi: 10.4103/1673-5374.177744.
Our preliminary proteomics analysis suggested that expression of microtubule-associated protein tau is elevated in the spinal cord after injury. Therefore, the first aim of the present study was to examine tau expression in the injured spinal cord. The second aim was to determine whether tau can regulate neural stem cell migration, a critical factor in the successful treatment of spinal cord injury. We established rat models of spinal cord injury and injected them with mouse hippocampal neural stem cells through the tail vein. We used immunohistochemistry to show that the expression of tau protein and the number of migrated neural stem cells were markedly increased in the injured spinal cord. Furthermore, using a Transwell assay, we showed that neural stem cell migration was not affected by an elevated tau concentration in the outer chamber, but it was decreased by changes in intracellular tau phosphorylation state. These results demonstrate that neural stem cells have targeted migration capability at the site of injury, and that although tau is not a chemokine for targeted migration of neural stem cells, intracellular tau phosphorylation/dephosphorylation can inhibit cell migration.
我们初步的蛋白质组学分析表明,微管相关蛋白tau在脊髓损伤后的表达会升高。因此,本研究的首要目的是检测损伤脊髓中tau的表达情况。第二个目的是确定tau是否能够调节神经干细胞迁移,这是成功治疗脊髓损伤的关键因素。我们建立了大鼠脊髓损伤模型,并通过尾静脉向其注射小鼠海马神经干细胞。我们使用免疫组织化学方法显示,损伤脊髓中tau蛋白的表达和迁移的神经干细胞数量显著增加。此外,通过Transwell实验,我们发现外室中升高的tau浓度不会影响神经干细胞迁移,但细胞内tau磷酸化状态的改变会使其迁移减少。这些结果表明,神经干细胞在损伤部位具有靶向迁移能力,并且尽管tau不是神经干细胞靶向迁移的趋化因子,但细胞内tau的磷酸化/去磷酸化可抑制细胞迁移。