Department of Pharmacy, Institute of Dermatology, Chinese Academy of Medical Sciences, Nanjing, Jiangsu 210001, P.R. China.
Central Laboratory of Yijishan Hospital, Wannan Medical College, Wuhu, Anhui 241001, P.R. China.
Mol Med Rep. 2017 Nov;16(5):7382-7390. doi: 10.3892/mmr.2017.7511. Epub 2017 Sep 19.
Macrophages possess the hallmark feature of plasticity, allowing them to undergo a dynamic transition between M1 and M2 polarized phenotypes. The aim of the present study was to screen for differentially-expressed genes (DEGs) that were associated with BALB/c murine macrophage polarization. The transcription profiles of three M1 and three M2 samples were obtained using microarray analysis. Based on the threshold of fold‑change >2.0 and P‑value <0.05, a total of 1,253 DEGs were identified, of which 696 were upregulated and 557 downregulated in M1 macrophages compared with M2 macrophages. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. A gene‑gene interaction network of the DEGs was constructed using the Search Tool for the Retrieval of Interacting Genes database. GO annotation identified three categories: Cellular component, molecular function and biological process, with 34 and 40 enrichment terms consisting of upregulated and downregulated DEGs, respectively. GO enrichment analysis of DEGs was primarily associated with protein binding, response to stimulus, cell differentiation, and regulation of biological process. KEGG enrichment identified 15 and four pathways involving upregulated and downregulated DEGs, respectively. Signaling pathway analysis revealed that these DEGs were mainly involved in apoptosis, hypoxia‑inducible factor (HIF) 1a pathway, innate immune system, tumor necrosis factor (TNF) signaling pathway, cytokine‑cytokine receptor interaction, and other signal transduction pathways. Interaction network analysis indicated that genes including TNF, interleukin (IL)‑6, IL‑1β, suppressor of cytokine signaling 3, nitric oxide synthase 2, HIF1a may serve key roles in macrophage polarization. The present study provided new insights into the role of genes in macrophage differentiation and polarization.
巨噬细胞具有可塑性的标志性特征，允许它们在 M1 和 M2 极化表型之间进行动态转变。本研究旨在筛选与 BALB/c 鼠巨噬细胞极化相关的差异表达基因 (DEG)。使用微阵列分析获得了三个 M1 和三个 M2 样本的转录谱。基于倍数变化 >2.0 和 P 值 <0.05 的阈值，共鉴定出 1253 个 DEG，其中 M1 巨噬细胞中 696 个上调，557 个下调与 M2 巨噬细胞相比。进行了基因本体 (GO) 功能和京都基因与基因组百科全书 (KEGG) 途径富集分析。使用 Search Tool for the Retrieval of Interacting Genes 数据库构建了 DEG 的基因-基因相互作用网络。GO 注释确定了三个类别：细胞成分、分子功能和生物过程，分别有 34 和 40 个富集术语包含上调和下调的 DEG。GO 富集分析显示，DEG 主要与蛋白结合、对刺激的反应、细胞分化以及生物过程的调节有关。KEGG 富集确定了涉及上调和下调 DEG 的 15 和 4 条途径。信号通路分析表明，这些 DEG 主要参与凋亡、缺氧诱导因子 (HIF) 1a 通路、固有免疫系统、肿瘤坏死因子 (TNF) 信号通路、细胞因子-细胞因子受体相互作用以及其他信号转导通路。互作网络分析表明，包括 TNF、白细胞介素 (IL)-6、IL-1β、细胞因子信号转导抑制因子 3、一氧化氮合酶 2、HIF1a 在内的基因可能在巨噬细胞极化中发挥关键作用。本研究为基因在巨噬细胞分化和极化中的作用提供了新的见解。
