Fn激活脊髓星形胶质细胞机制的研究

After spinal cord injury，the activation of astrocytes is a significant factor which interferes the recovery of spinal cord function. Previous studies have shown that Fn could activate the astrocytes, but the mechanism remains poorly understand. Our recent researches have discovered that Fn could induce the phosphorylation of EGFR. So in this subject, we want to finish the following researches via EGFR signaling pathway: 1) the function of Src and MMP in the transactviation of EGFR induced by Fn; 2) the activation of MEK/ERK and PI3K/Akt mediated by Fn via the transactivation of EFGF, and the influence of Fn on the protein expression, proliferation and migration ability of astrocytes; 3) the function of EGFR transactivation in the expression and effection of P2Y1 receptor regulated by Fn, according to our recent results of the expression of P2Y1 upregulated by Fn-f and the close relationship between EGFR and P2Y. Through this project, we hope to discover the exact mechanism of the astrocytes activated by Fn, have an insight into the mechanism of the astrocytes activation after spinal cord injury, and promote the spinal cord nerve function recovery.

脊髓损伤后，星形胶质细胞的活化被认为是阻碍脊髓神经功能恢复的重要因素。研究表明纤连蛋白（Fn）可以激活星形胶质细胞，但其作用机制不明确。我们前期研究发现Fn可增加脊髓星形胶质细胞表皮生长因子受体（EGFR）的磷酸化水平，因此本课题拟通过EGFR信号通路进行以下研究：1)Fn激活EGFR的机制，即Src激酶和基质金属蛋白酶在其中的作用;2)Fn诱导EGFR磷酸化后对星形胶质细胞的影响，即EGFR活化后MEK/ERK 和PI3K/Akt 两条信号传导通路的信号传导，以及对星形胶质细胞蛋白表达、增殖和迁移能力的影响;3)我们还发现Fn具有上调P2Y1受体表达的作用，EGFR与P2Y有着密切的联系，本课题还将探讨EGFR通路在Fn调节P2Y1受体表达及功能中所起的作用。希望通过本课题的研究发现Fn激活脊髓星形胶质细胞的机制，为抑制脊髓损伤后星形胶质细胞的活化以及促进脊髓神经功能恢复提出新的见解。

本课题计划研究脊髓损伤后星形胶质细胞活化的机制，主要探讨纤维粘连蛋白（Fn）激活脊髓星形胶质细胞的具体机制。项目按计划执行。发现Fn通过与其膜受体整合素alpha1beta5结合激活了Akt和ERK，增加了表皮生长因子受体（EGFR）的磷酸化，进而促进了细胞的增殖。同时本课题还发现Fn有增加P2Y1表达的作用，增强了ATP激活星形胶质细胞的作用，即发现了Fn与ATP对于星形胶质细胞的协同作用。而且对ATP激活星形胶质细胞的机制进行了深入研究，发现FOXO3a和Sox2、9参与了该过程。已有3篇相关论文发表，均为SCI 收录。