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剖析类风湿关节炎中滑膜巨噬细胞的失衡

Dissecting the Imbalance of Synovial Macrophages in Rheumatoid Arthritis.

作者信息

Li Qing, Liu Wenping, Wang Jibo

出版信息

Altern Ther Health Med. 2023 Oct;29(7):434-439.

Abstract

OBJECTIVE

This study sought to identify candidate genes of rheumatoid arthritis (RA) synovial macrophages using bioinformatics and to explore their pathways in the pathogenesis of RA.

METHODS

The microarray datasets GSE10500 and GSE97779 were obtained from the Gene Express Omnibus and analyzed with synovial macrophages of 14 RA patients and 8 healthy donors. The researchers used R software to identify differentially expressed genes and determine functional enrichment pathways. A protein-protein interaction network was then constructed using STRING and Cytoscape. Gene expression was validated with the GSE71370 dataset and RT-qPCR analysis.

RESULTS

102 DEGs were identified in RA synovial macrophages relative to normal samples. Of these, 72 were upregulated; 30 were downregulated. GO and KEGG pathway analyses suggested that DEGs mainly regulated the immune response and signaling pathways associated with inflammatory activation, apoptosis, and cancer. The top five hub genes and top 1 gene module from the PPI network of DEGs were VEGFA, MMP9, FN1, IGF1, CXCL9, ISG20, RSAD2, IFI27, GBP2, and GBP1. The GSE71370 dataset and RT-qPCR analysis showed that CXCL9 and GBP1 were significantly upregulated (P ≤ .05).

CONCLUSIONS

CXCL9 and GBP1 may contribute to RA pathogenesis and serve as potential biomarkers and therapeutic targets for RA.

摘要

目的

本研究旨在利用生物信息学方法鉴定类风湿关节炎(RA)滑膜巨噬细胞的候选基因,并探索其在RA发病机制中的相关通路。

方法

从基因表达综合数据库(Gene Express Omnibus)获取微阵列数据集GSE10500和GSE97779,并对14例RA患者和8例健康供体的滑膜巨噬细胞进行分析。研究人员使用R软件鉴定差异表达基因并确定功能富集通路。然后利用STRING和Cytoscape构建蛋白质-蛋白质相互作用网络。通过GSE71370数据集和RT-qPCR分析验证基因表达情况。

结果

相对于正常样本,在RA滑膜巨噬细胞中鉴定出102个差异表达基因(DEG)。其中,72个上调,30个下调。基因本体(GO)和京都基因与基因组百科全书(KEGG)通路分析表明,DEG主要调控与炎症激活、细胞凋亡和癌症相关的免疫反应和信号通路。DEG的蛋白质-蛋白质相互作用网络中排名前五位的枢纽基因和排名第一的基因模块分别是血管内皮生长因子A(VEGFA)、基质金属蛋白酶9(MMP9)、纤连蛋白1(FN1)、胰岛素样生长因子1(IGF1)、CXC趋化因子配体9(CXCL9)、干扰素刺激基因20(ISG20)、维甲酸诱导蛋白I(RSAD2)、干扰素诱导蛋白27(IFI27)、鸟苷结合蛋白2(GBP2)和鸟苷结合蛋白1(GBP1)。GSE71370数据集和RT-qPCR分析表明,CXCL9和GBP1显著上调(P≤0.05)。

结论

CXCL9和GBP1可能参与RA的发病机制,可作为RA潜在的生物标志物和治疗靶点。

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