项目名称: CXCL12/CXCR4通过ERK和PI3K信号通路介导少突胶质前体细胞促进轴突再髓鞘化的机制研究
项目编号: No.81471262
项目类型: 面上项目
立项/批准年度: 2015
项目学科: 医药、卫生
项目作者: 任先军
作者单位: 中国人民解放军第三军医大学
项目金额: 70万元
中文摘要: 轴突脱髓鞘改变是脊髓损伤的重要病理变化,前期研究表明,移植少突胶质前体细胞(OPCS)能够促进损伤轴突再髓鞘化。但是再生髓鞘的形态和厚度存在差别,再髓鞘化的确切机制不清楚。OPC中ERK和PI3K通路激活后可以增强与髓鞘形成相关的MBP及PLP的表达;脊髓损伤后细胞间质内CXCL12升高,并与OPCs的迁移和分化关系密切;而ERK和PI3K通路是CXCL12/CXCR4分子信号常见的下游通路,CXCL12可以通过ERK和PI3K通路参与神经前体细胞的生理过程。因此本课题推测:在OPCs参与再髓鞘化的过程中,CXCL12是激活ERK和PI3K通路的关键因子,通过ERK和PI3K通路介导OPCs中MBP与PLP的高表达,对再生髓鞘形态及厚薄发挥重要的调控作用。课题拟采用免疫细胞化学技术、增强及阻断干预、体外实验及体内移植等手段,阐明CXCL12/CXCR4在介导OPC参与轴突再髓鞘化的作用机制
中文关键词: 再髓鞘化;少突胶质前体细胞移植;CXCL12/CXCR4信号通路;ERK信号通路;PI3K;信号通路
英文摘要: Axonal demyelination of spinal cord injury is an important pathological changes, seriously affecting the retention function of axons. Transplantation of oligodendrocyte precursor cells (OPCS) can promote axonal remyelination, however remyelination exact mechanism is not very clear, thin and short myelin regeneration, and the original form and function of myelin have certain distinction. Therefore, to clarify the mechanism of axonal remyelination has important implications for the treatment of spinal cord injury. There are experiments showed increased expression of CXCL12 after spinal cord injury, and the migration and differentiation of OPCs closely. RAF-MEK-ERK and PI3K/Akt pathways involved in remyelination of axons and is CXCL12/CXCR4 common downstream pathways. This topic speculate: CXCL12 by interacting with its receptor CXCR4, not only to mediate transplant directional migration and proliferation of OPCs in vivo, and can be directly involved in remyelination of axons regenerated through ERK and PI3K pathways affect axon myelination. Studies using a variety of techniques intended to clarify the role of CXCL12/CXCR4 molecular signals in myelination of axons in for the treatment of spinal cord injury provides a new idea.
英文关键词: Remyelination;oligodendrocyte precusor cell transplantation;CXCL12/CXCR4 Signaling pathway;ERK Signaling pathway;PI3K Signaling pathway