基于生物信息学考察骨髓干细胞治疗缺血性脑卒中的潜在机制

Potential mechanisms of bone marrow stem cells in the treatment of ischemic stroke based on bioinformatics

背景:在治疗缺血性脑卒中过程中,干细胞疗法已经获得了广泛的关注,然而对于其所涉及到的复杂调控机制,相关研究较少。目的:应用生物信息学方法研究骨髓干细胞治疗缺血性脑卒中的分子调控机制。方法:应用DisGeNET数据库调取缺血性脑卒中的背景网络,再通过GEO在线数据库获得骨髓干细胞治疗前后差异表达明显的基因;再将这些基因对上述背景网络进行打靶处理,最终获得与缺血性脑卒中相关的靶点,应用DAVID和String数据库分析这些靶标基因之间的关系。结果与结论:(1)DisGeNET数据库可调取的缺血性脑卒中的调控分子靶标共计393个;GEO数据库获得的骨髓干细胞治疗缺血性脑卒中的数据集内,与缺血性脑卒中发病密切相关的分子靶点共计39个,其中下调的分子靶点包含FBN1,NPY,MMP10,ITGB3,GLA等30个,上调的分子靶点包含EZH2,ESR1,IL16,LGALS2等9个;(2)由String数据库获得其对应的互作关系后,可获得上述39个靶点的互作关系,共有10个节点大于平均节点度,分别为TP53,SPP1,VCAM1,PTGS2,ESR1,F3,TIMP2,CD40,EZH2,ITGB3,除了ESR1和EZH2是上调基因外,其余均为下调基因;(3)在该过程中,主要调控的通路有血管剪切力调节及松弛素信号通路;IL-7、NFKB等炎症相关的信号通路;神经活性配体-受体、同种异体排斥反应等信号通路。

BACKGROUND: Stem cell therapy has received sustained attention in the treatment of prognosis of ischemic stroke. However, little research has been done on its complex regulatory mechanism. OBJECTIVE: To study the molecular regulatory network of stem cell therapy for ischemic stroke by bioinformatics. METHODS: DisGeNET database was used to collect the background network of ischemic stroke, and then GEO online database was used to obtain differentially expressed genes before and after treatment with bone marrow stem cells. Gene targeting was performed in the above genes to obtain stroke-related targets. DAVID and STING databases were used to analyze the relationship between these target genes. RESULTS AND CONCLUSION: In the DisGeNET database, there were 393 molecular targets for ischemic cerebrovascular accident regulation. Thirty-nine molecular targets were confirmed to be related to ischemic cerebrovascular accident in the data set of stem cell therapy in the GEO database. Among them, 30 were down-regulated, including FBN1, NPY, MMP10, ITGB3, and GLA;and 9 were up-regulated, including EZH2, ESR1, IL16, and LGALS2. (2) Based on the corresponding interaction relation described in String database, the above 39 targets could be obtained. There were 10 nodes with a greater node degree, namely TP53, SPP1, VCAM1, PTGS2, ESR1, F3, TIMP2, CD40, EZH2, and ITGB3. Except for up-regulated genes, ESR1 and EZH2, the others were down-regulated genes. (3) The main regulatory pathways involved in this process included: vascular shear stress regulation and relaxin signaling pathways directly acting on blood vessels;inflammatory-related signaling pathways such as IL-7, NFKB;neuroactive ligand-receptor, allograft rejection and other signaling pathways.