自体骨髓干细胞移植对脊髓损伤潜在分子靶点治疗机制的生物信息学分析  

Potential molecular targets and therapeutic mechanisms underlying transplantation of autologous bone marrow stem cells for the treatment of spinal cord injury based on bioinformatics

作　　者：荀翀 王强[1] 李长洲[1] 刘晓峰[1] Xun Chong;Wang Qiang;Li Changzhou;Liu Xiaofeng(First Affiliated Hospital of Dalian Medical University,Dalian 116011,Liaoning Province,China)

机构地区：[1]大连医科大学附属第一医院,辽宁省大连市116011

出　　处：《中国组织工程研究》2020年第31期4927-4933,共7页Chinese Journal of Tissue Engineering Research

基　　金：辽宁省自然科学基金指导计划(20170540606)。

摘　　要：背景:以往骨髓间充质干细胞治疗脊髓损伤获得了较好的临床效果,但现有的研究多集中于该过程的病理生理变化,而对所涉及到的分子靶点及相应潜在通路的调控机制研究不足。目的:应用生物信息学方法,考察骨髓间充质干细胞治疗脊髓损伤的潜在分子靶点及信号通路。方法:在GEO数据库内调取骨髓间充质干细胞对脊髓损伤治疗的芯片组数据,再将其映射于由CTD数据库所获得的脊髓损伤疾病背景网络,最终得到骨髓间充质干细胞治疗脊髓损伤过程中的差异表达基因,以sting构建其蛋白-蛋白互作网络,再应用Cytoscape分析其网络特性,获得该过程中的核心差异基因,最后,在WebGestalt网站内对上述基因进行功能富集,以获得上述分子靶点的分子功能及相应的信号通路。结果与结论:①GEO芯片的数据结果显示,骨髓间充质干细胞治疗脊髓损伤的核心分子靶点共有126个,其中有60个在CTD数据库上有过报道;②根据sting及cytoscape的结果显示,其形成的蛋白-蛋白互作网络内,共有57个节点,而所涉及到的核心靶点的10个靶点为MAPK3、肿瘤坏死因子、白细胞介素6、CASP3、血管内皮生长因子A、MAPK1、趋化因子2、白细胞介素1β、原癌基因蛋白及胰岛素样生长因子1等;③在该过程中,主要调控的通路有白细胞介素17、MAPK、肿瘤坏死因子、Toll样受体及NOD样受体等重要的炎症信号通路;④该过程最重要的2个方面分别是对炎症反应所介导神经损伤的抑制及受损神经的营养修复。BACKGROUND:Bone marrow mesenchymal stem cells have achieved good clinical effect in the treatment of spinal cord injury.However,most of the existing studies focus on the pathophysiological changes,and less is reported on the molecular regulatory mechanism involved.OBJECTIVE:To study the potential molecular targets and signal pathway related to the use of bone marrow mesenchymal stem cells in the treatment of spinal cord injury based on bioinformatics analysis.METHODS:The microarray data of bone marrow mesenchymal stem cells for spinal cord injury treatment were retrieved from GEO database and then mapped to the background network of spinal cord injury obtained from CTD database.Finally,the differentially expressed genes were obtained.A protein-protein interaction network constructed by sting was used to analyze its network characteristics using Cytoscape and obtain the core molecular targets in the process.Finally,the molecular functions and signal pathways of the above molecular targets were analyzed by functional enrichment of the above genes on the website of WebGestalt.RESULTS AND CONCLUSION:According to the data of GEO chip,there are 126 core molecular targets in the treatment of spinal cord injury by bone marrow mesenchymal stem cells,60 of which have been reported in CTD database.According to the results of sting and Cytoscape,there are 57 nodes in the protein-protein interaction network,among which 10 core targets are MAPK3,tumor necrosis factor,interleukin 6,CASP3,vascular endothelial growth factor A,MAPK1,CCL2,interleukin 1B,proto-oncogene protein,insulin-like growth factor 1.In this process,the main regulatory pathways are interleukin 17,MAPK,tumor necrosis factor,Toll-like receptor and nod-like receptor.The two most important aspects of this process are the inhibition of inflammatory response mediated nerve damage and the nutritional repair of damaged nerve.

关 键 词：生物信息学 脊髓损伤 干细胞疗法 骨髓间充质干细胞 分子机制 蛋白互作网络 神经保护 神经修复 

分 类 号：R459.9[医药卫生—治疗学] R496[医药卫生—临床医学]