Objectives: To study the gene expression of adipose tissue CD14+ cells in patients with Type 2 diabetes mellitus (T2DM) based on chip data, screen differentially expressed genes, and analyze their relationship with the environmental factors.
Methods: The data of GSE54350 were obtained from the public database of gene expression profiling. The data were pre-processed by Network Analyst, String 11.0, Cytoscape 3.7.1, and other analytical software. The differentially expressed genes were analyzed by gene ontology biological function and kyoto encycopedia of genes and genomes (KEGG) signaling pathway to establish differential gene protein interaction network, transcription factor-gene regulatory network, microRNA-gene regulatory network, environmental factors-gene regulatory network, and other interaction systems.
Results: The gene expression pattern of CD14+ cells in adipose tissue of obese T2DM patients was significantly different from that of obese non-T2DM patients. There were 19 differentially expressed genes with up-regulation. The differentially expressed genes were mainly involved in ARP2/3 complex regulation of actin cytoskeleton, positively associated with biological processes such as protein complex assembly, and involved in the phagocytic Fcγ receptor signaling pathways and receptor family signaling pathways. The protein-protein interaction networks showed that TNF was the core protein node. The microRNA-gene regulatory network showed that hsa-mir-124-3p interacted with differentially expressed genes; TNF, KYNU, RCAN1 and other related genes all interacted with environmental factors.
Conclusions: The gene expression of adipose tissue CD14+ cells are significantly changed in obese T2DM patients. TNF may play an important role in the process of obesity affecting the immune status of T2DM patients. Multiple microRNAs, transcription factors, and environmental factors also play a role in the above process. This study provides new material and new ideas for further exploration of the impact of obesity on T2DM patients.
目的: 基于芯片数据研究2型糖尿病(Type 2 diabetes mellitus，T2DM)患者脂肪组织CD14+细胞的基因表达情况，筛选差异表达基因(differentially expressed genes，DEGs)，利用生物信息学方法分析肥胖影响T2DM患者免疫状况的分子机制及环境因子对该机制的影响。方法: 从基因表达谱公共数据库中获取数据集GSE54350，采用Network analyst、String11.0、Cytoscape 3.7.1等分析软件对数据进行预处理，筛选数据库的DEGs，进行基因功能(gene ontology，GO)与KEGG(kyoto encycopedia of genes and genomes)信号通路富集分析，建立DEGs蛋白质-蛋白质互作网络、转录因子-基因调控网络、microRNA-基因调控网络、环境因子-基因调控网络等交互作用系统。结果: 肥胖型T2DM患者脂肪组织中CD14+细胞的基因表达模式与肥胖非T2DM患者有显著差异，共有19个 DEGs，表达均上调；DEGs主要参与ARP2/3复合体调控肌动蛋白细胞骨架、正向调节蛋白质复合物组装等生物学过程，并涉及与吞噬作用相关的Fcγ受体信号转导途径和受体家族信号通路；蛋白质-蛋白质互作网络显示TNF为核心蛋白节点；microRNA-基因调控网络显示hsa-miR-124-3p与DEGs具有交互作用；TNF、KYNU、RCAN1等相关基因均与环境因子有交互作用。结论: 肥胖型T2DM患者脂肪组织CD14+细胞的基因表达发生显著改变，TNF可能在肥胖影响T2DM患者免疫状况过程中发挥重要作用，多个microRNA、转录因子和环境因子在上述过程中也起一定作用。这为深入探索肥胖对T2DM患者的影响提供了新素材和思路。.
Keywords: Type 2 diabetes mellitus; environmental factors, bioinformatics; immunity; obesity.