Dataset Information

MicroRNA Expression Profiling in Psoriatic Arthritis.

ABSTRACT: Background:Psoriatic arthritis (PsA) is an inflammatory arthritis, characterized by bone erosions and new bone formation. MicroRNAs (miRNAs) are key regulators of the immune responses. Differential expression of miRNAs has been reported in several inflammatory autoimmune diseases; however, their role in PsA is not fully elucidated. We aimed to identify miRNA expression signatures associated with PsA and to investigate their potential implication in the disease pathogenesis. Methods:miRNA microarray was performed in blood cells of PsA patients and healthy controls. miRNA pathway analyses were performed and the global miRNA profiling was combined with transcriptome data in PsA. Deregulation of selected miRNAs was validated by real-time PCR. Results:We identified specific miRNA signatures associated with PsA patients with active disease. These miRNAs target pathways relevant in PsA, such as TNF, MAPK, and WNT signaling cascades. Network analysis revealed several miRNAs regulating highly connected genes within the PsA transcriptome. miR-126-3p was the most downregulated miRNA in active patients. Noteworthy, miR-126 overexpression induced a decreased expression of genes implicated in PsA. Conclusions:This study sheds light on some epigenetic aspects of PsA identifying specific miRNAs, which may represent promising candidates as biomarkers and/or for the design of novel therapeutic strategies in PsA.

SUBMITTER: Pelosi A

PROVIDER: S-EPMC5937573 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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MicroRNA Expression Profiling in Psoriatic Arthritis.

Pelosi Andrea A Lunardi Claudio C Fiore Piera Filomena PF Tinazzi Elisa E Patuzzo Giuseppe G Argentino Giuseppe G Moretta Francesca F Puccetti Antonio A Dolcino Marzia M

BioMed research international 20180423

<h4>Background</h4>Psoriatic arthritis (PsA) is an inflammatory arthritis, characterized by bone erosions and new bone formation. MicroRNAs (miRNAs) are key regulators of the immune responses. Differential expression of miRNAs has been reported in several inflammatory autoimmune diseases; however, their role in PsA is not fully elucidated. We aimed to identify miRNA expression signatures associated with PsA and to investigate their potential implication in the disease pathogenesis.<h4>Methods</h ...[more]

PMID: 29850558

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Project description:BackgroundPsoriatic arthritis (PsA) is an inflammatory arthritis whose pathogenesis is poorly understood; it is characterized by bone erosions and new bone formation. The diagnosis of PsA is mainly clinical and diagnostic biomarkers are not yet available. The aim of this work was to clarify some aspects of the disease pathogenesis and to identify specific gene signatures in paired peripheral blood cells (PBC) and synovial biopsies of patients with PsA. Moreover, we tried to identify biomarkers that can be used in clinical practice.MethodsPBC and synovial biopsies of 10 patients with PsA were used to study gene expression using Affymetrix arrays. The expression values were validated by Q-PCR, FACS analysis and by the detection of soluble mediators.ResultsSynovial biopsies of patients showed a modulation of approximately 200 genes when compared to the biopsies of healthy donors. Among the differentially expressed genes we observed the upregulation of Th17 related genes and of type I interferon (IFN) inducible genes. FACS analysis confirmed the Th17 polarization. Moreover, the synovial trascriptome shows gene clusters (bone remodeling, angiogenesis and inflammation) involved in the pathogenesis of PsA. Interestingly 90 genes are modulated in both compartments (PBC and synovium) suggesting that signature pathways in PBC mirror those of the inflamed synovium. Finally the osteoactivin gene was upregulared in both PBC and synovial biopsies and this finding was confirmed by the detection of high levels of osteoactivin in PsA sera but not in other inflammatory arthritides.ConclusionsWe describe the first analysis of the trancriptome in paired synovial tissue and PBC of patients with PsA. This study strengthens the hypothesis that PsA is of autoimmune origin since the coactivity of IFN and Th17 pathways is typical of autoimmunity. Finally these findings have allowed the identification of a possible disease biomarker, osteoactivin, easily detectable in PsA serum.

Dataset Information

MicroRNA Expression Profiling in Psoriatic Arthritis.

Publications

MicroRNA Expression Profiling in Psoriatic Arthritis.

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