Abstract
Background 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. Methods 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. Results 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. Conclusions 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.
Highlights
Behçet’s disease (BD) is a rare and chronic multisystem disease characterized by a triple-symptom complex of recurrent oral aphthous ulcers, genital ulcers, and uveitis
Since a global miRNA expression analysis in BD with an updated coverage of miRNA sequences has not been performed yet, we wanted to provide a careful description of miRNAs associated with BD by interrogating the transcription of a large amount of different microRNA sequences in BD peripheral blood mononuclear cells (PBMCs) by microarray strategy
The aim of our work is to provide a compiled description of miRNAs associated with BD using an array able to query a very large number of transcripts in the attempt to dissect the possible regulatory effects exerted by these molecules on the molecular pathways relevant for the disease pathogenesis
Summary
Behçet’s disease (BD) is a rare and chronic multisystem disease characterized by a triple-symptom complex of recurrent oral aphthous ulcers, genital ulcers, and uveitis. Behçet’s disease (BD) is a chronic inflammatory multisystem disease characterized by oral and genital ulcers, uveitis, and skin lesions. We aimed to identify miRNA expression signatures associated with BD and to investigate their potential implication in the disease pathogenesis. 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. 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
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