自发性脊髓再生中MIF的非炎性功能研究

项目名称： 自发性脊髓再生中MIF的非炎性功能研究

项目编号： No.31471011

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 神经、认识与心理学

项目作者： 王勇军

作者单位： 南通大学

项目金额： 86万元

中文摘要： 过度激活的炎症反应是脊髓继发性损伤的关键因素之一，诸多研究表明，巨噬细胞迁移抑制分子MIF是触发炎症反应的核心分子。有趣的是，低等脊椎动物脊髓损伤后却能够规避炎症反应再生脊髓，那么MIF在自发性脊髓再生中是如何消减炎症反应，它的非炎性功能及信号调节机制又是什么？我们前期工作发现，MIF没有引发多疣壁虎断尾脊髓的炎症反应；MIF在断尾末端组织和损伤脊髓中通过时空差异表达，对炎症细胞和胶质细胞产生截然不同的细胞学效应，降低炎症反应，调节脊髓再生。在此基础上，本课题拟深入阐明其对脊髓中不同细胞的影响，揭示其细胞学效应的分子调控机制；在体干预损伤脊髓中MIF以及下游通路分子的表达，检测其对脊髓再生的影响；结合转录组测序和核心信号流分析模型，寻找调节MIF时空差异表达以规避炎症反应的关键分子，并体内外验证。通过对MIF促炎分子的功能和信号途径的比较学研究，为控制高等哺乳动物脊髓继发性损伤提供线索。

中文关键词： 神经再生；胶质细胞；神经元；炎症；巨噬细胞

英文摘要： Uncontrolled, excessive inflammation contributes to the second tissue damage of traumatic spinal cord, and macrophage migration inhibitory factor (MIF) has been found to be a key molecule involved in the process. It is interesting to note that several regenerative-competent vertebrates have evolved to circumvent the second damages during the spontaneous spinal cord regeneration.So, the question arises as to how MIF attenuates inflammatory responses and what the non-inflammatory function of MIF is, as well as what the underlying mechanisms are. Our previous study revealed that MIF did not trigger the inflammatory response of gecko injured spinal cord. MIF decreased the inflammation and promoted the spinal cord regeneration by differential spatial-temporal expression in the tail stump and injured spinal cord following tail amputation, where it acted reverse functions on the macrophages and glial cells. To address its special functions in the spontaneous spinal cord regeneration, we are going to shed light on the effects of MIF on the various cells in the spinal cord and the underlying signal mechanisms; we will further exmaine the effects on the spinal cord regeneration by interference of MIF and its co-factors; we also try to find out the key regulators of MIF, which is differentially expressed in order to circumvent the inflammatory reaction, by transcriptome sequence and gene network analysis. At last, we are going to perform the in vivo validation to the important regulators. By the comparative studies of pro-inflammatory cytokine MIF, we attempt to provide some clues for the control of the second tissue damage of traumatic spinal cord in mammals.

英文关键词： neural regeneration;glial cells;neuron;inflammation;macrophage