Immunology Area, Pediatric Hospital Bambino Gesù, Viale San Paolo 15, 00146 Rome, Italy.
Department of Experimental Medicine-Section of Histology, University of Genova, Via G.B. Marsano 10, 16132 Genova, Italy.
J Immunol Res. 2018 May 7;2018:2405150. doi: 10.1155/2018/2405150. eCollection 2018.
Behçet's disease (BD) is a chronic inflammatory multisystem disease characterized by oral and genital ulcers, uveitis, and skin lesions. MicroRNAs (miRNAs) are key regulators of immune responses. Differential expression of miRNAs has been reported in several inflammatory autoimmune diseases; however, their role in BD is not fully elucidated. We aimed to identify miRNA expression signatures associated with BD and to investigate their potential implication in the disease pathogenesis.
miRNA microarray analysis was performed in blood cells of BD patients and healthy controls. miRNA expression profiles were analyzed using Affymetrix arrays with a comprehensive coverage of miRNA sequences. Pathway analyses were performed, and the global miRNA profiling was combined with transcriptoma data in BD. Deregulation of selected miRNAs was validated by real-time PCR.
We identified specific miRNA signatures associated with BD patients with active disease. These miRNAs target pathways relevant in BD, such as TNF, IFN gamma, and VEGF-VEGFR signaling cascades. Network analysis revealed several miRNAs regulating highly connected genes within the BD transcriptoma.
The combined analysis of deregulated miRNAs and BD transcriptome sheds light on some epigenetic aspects of BD identifying specific miRNAs, which may represent promising candidates as biomarkers and/or for the design of novel therapeutic strategies in BD.
贝赫切特病（BD）是一种慢性炎症性多系统疾病，其特征为口腔和生殖器溃疡、葡萄膜炎和皮肤损伤。微小 RNA（miRNA）是免疫反应的关键调节因子。在几种炎症性自身免疫性疾病中已经报道了 miRNA 的差异表达；然而，其在 BD 中的作用尚未完全阐明。我们旨在确定与 BD 相关的 miRNA 表达特征，并研究其在疾病发病机制中的潜在作用。
通过 miRNA 微阵列分析对 BD 患者和健康对照者的血细胞进行分析。使用 Affymetrix 芯片对 miRNA 表达谱进行分析，该芯片全面覆盖了 miRNA 序列。进行了通路分析，并将全局 miRNA 分析与 BD 中的转录组数据相结合。通过实时 PCR 验证选定 miRNA 的失调。
我们确定了与活动期 BD 患者相关的特定 miRNA 特征。这些 miRNA 靶向与 BD 相关的通路，如 TNF、IFNγ 和 VEGF-VEGFR 信号级联。网络分析显示了几个 miRNA 调节 BD 转录组中高度连接的基因。
失调 miRNA 和 BD 转录组的联合分析揭示了 BD 的一些表观遗传方面，确定了一些可能作为生物标志物和/或用于 BD 新型治疗策略设计的有前途的候选 miRNA。
