Integrated analysis of gene expression profiles identifies transcription factors potentially involved in psoriasis pathogenesis
Integrated analysis of gene expression profiles identifies transcription factors potentially involved in psoriasis pathogenesis
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基因表达谱的综合分析确定了可能参与银屑病发病机制的转录因子
DOI：
10.1002/jcb.28525
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发表时间：
2019
影响因子：
4
通讯作者：
Zheng Fang
中科院分区：
文献类型：
--
作者：
Zeng Fanfan;Liu Hongbo;Lu Di;Liu Qianqian;Chen Huoying;Zheng Fang
银屑病是一种常见的炎症性皮肤病，由天然免疫系统和获得性免疫系统中的细胞和分子介导。最近，基因表达谱分析揭示了大量与银屑病免疫相关的差异表达基因(Deg)。然而，这些DEG与其转录调控机制之间的联系还没有完全阐明。本研究利用生物信息学工具对几个银屑病基因表达数据集进行了系统的分析，以揭示调节免疫相关基因表达的重要转录因子，从而进一步加深我们对银屑病发病机制的理解。在银屑病中发现了编码趋化因子、细胞因子、抗菌肽和角蛋白的常见deg，并且这些deg之间存在广泛的相关性。几种常见的与DEGS启动子结合的转录因子，包括已知的信号转导和转录激活因子1(STAT1)、STAT3、活化B细胞核因子κ轻链增强子(NF-κB)以及Ets同源因子(EHF)、Fos样抗原1(FOSL1)和Forkhead box C1(FOXC1)在银屑病皮损中与这些DEGS呈正相关，其中FOXC1与大多数DEGS呈负相关。在银屑病中，DEGS的表达下降伴随着STAT1、流行性出血热、FOSL1、STAT3和NFKB1的下调，而FOXC1在阻断白介素17(IL-17)或肿瘤坏死因子α信号转导时上调。此外，银屑病患者IL-37表达下调与Th1应答相关的STAT1和CXCL10呈负相关。这些结果表明，转录因子在银屑病的发病机制中起着重要作用，干扰关键因子的活性可能是治疗银屑病的一种有前途的策略。
Psoriasis is a common inflammatory skin disease mediated by cells and molecules in both the innate and adaptive immune systems. Recently, gene expression profile analysis revealed a large set of immune‐related differentially expressed genes (DEGs) in psoriasis. However, the associations between these DEGs and their transcriptional regulation mechanisms have not been completely elucidated. In this study, several psoriasis Gene Expression Omnibus data sets were systematically analyzed using bioinformatics tools to uncover important transcription factors (TFs) that regulate the expression of immune‐related DEGs and further enhance our understanding of psoriasis pathogenesis. Common DEGs encoding chemokines, cytokines, antimicrobial peptides, and keratins were identified in psoriasis, and extensive correlations existed among these DEGs. Several common TFs that bind the promoters of the DEGs, including the well‐known signal transducer and activator of transcription 1 (STAT1), STAT3, and nuclear factor κ‐light‐chain‐enhancer of activated B cells (NF‐κB) as well as ETS homologous factor (EHF), Fos‐like antigen 1 (FOSL1), and Forkhead box C1 (FOXC1), which are rarely studied in psoriasis, were also identified.STAT1,EHF,FOSL1,STAT3, andNFKB1were positively correlated with these DEGs in psoriasis lesions, whereasFOXC1was negatively correlated with most DEGs. The decreased expression of the DEGs was accompanied by the downregulation ofSTAT1,EHF,FOSL1,STAT3, andNFKB1and the upregulation ofFOXC1upon blocking interleukin 17 (IL‐17) or tumor necrosis factor α signaling in psoriasis. Additionally, the downregulation ofIL37in psoriasis was negatively correlated withSTAT1andCXCL10, which are associated with Th1 responses. These results suggest that TFs play an important role in the pathogenesis of psoriasis, and interfering with the activity of key TFs may be a promising therapeutic strategy for psoriasis.