Department of Orthopedics, Third Military Medical University (Army Medical University), Chongqing 400037, P.R. China.
Department of Ultrasound, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing 400037, P.R. China.
Mol Med Rep. 2018 Nov;18(5):4374-4380. doi: 10.3892/mmr.2018.9444. Epub 2018 Sep 3.
Demyelination is a nervous system disease in which the myelin sheaths of neurons are damaged due to inflammatory reactions, inherited abnormalities or trauma. This damage impairs the conduction of signals in the affected nerves, which in turn causes deficiencies in sensation, movement and cognition. Oligodendrocyte precursor cells (OPCs) are able to induce remyelination. However, the remyelination is suboptimal due to the limited migration of OPCs. In the present study, neonatal OPCs were isolated from rats for the investigation of the role of C‑X‑C motif chemokine ligand 12 (CXCL12), an important chemokine, in mediating the migration ability of OPCs. The present results demonstrated that CXCL12 stimulation markedly promoted the migration of OPCs and activated the dual specificity mitogen‑activated protein kinase kinase 1 (MEK)/extracellular signal‑regulated kinase (ERK) and phosphoinositide 3‑kinase (PI3K)/RAC‑α serine/threonine‑protein kinase (AKT) pathways. Knockdown of C‑X‑C motif chemokine receptor 4 (CXCR4; a receptor of CXCL12) reversed the CXCL12‑induced migration of OPCs and blocked the MEK/ERK and PI3K/AKT pathways. In addition, specific inhibitors of the MEK/ERK and PI3K/AKT pathways significantly reduced the migration of OPCs. Based on these findings, it was concluded that CXCL12 may induce the migration of OPCs through the CXCR4‑activated MEK/ERK and PI3K/AKT pathways. The results of the present study support the manipulation of CXCL12‑mediated OPC migration to improve remyelination.
脱髓鞘是一种神经系统疾病，其特征是神经元的髓鞘由于炎症反应、遗传异常或创伤而受损。这种损伤会损害受影响神经中的信号传导，进而导致感觉、运动和认知功能缺陷。少突胶质前体细胞（OPC）能够诱导髓鞘再生。然而，由于 OPC 的迁移能力有限，髓鞘的再生并不理想。在本研究中，从大鼠中分离出新生 OPC 以研究 C-X-C 基序趋化因子配体 12（CXCL12）作为一种重要的趋化因子在调节 OPC 迁移能力中的作用。本研究结果表明，CXCL12 刺激可显著促进 OPC 的迁移，并激活双特异性丝裂原活化蛋白激酶激酶 1（MEK）/细胞外信号调节激酶（ERK）和磷酸肌醇 3-激酶（PI3K）/ Rac-α 丝氨酸/苏氨酸蛋白激酶（AKT）通路。敲低 C-X-C 基序趋化因子受体 4（CXCR4；CXCL12 的受体）可逆转 CXCL12 诱导的 OPC 迁移，并阻断 MEK/ERK 和 PI3K/AKT 通路。此外，MEK/ERK 和 PI3K/AKT 通路的特异性抑制剂可显著减少 OPC 的迁移。基于这些发现，可以得出结论，CXCL12 可能通过 CXCR4 激活的 MEK/ERK 和 PI3K/AKT 通路诱导 OPC 的迁移。本研究的结果支持对 CXCL12 介导的 OPC 迁移进行调控以改善髓鞘再生。
