Journal
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
Volume 31, Issue 2, Pages 312-322Publisher
WILEY-BLACKWELL
DOI: 10.1111/jdv.13861
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Funding
- European Commission-European Regional Development Fund (ERDF/FEDER)
- Junta de Andalucia (JA), Consejerias de Innovacion-Ciencia-Empresa y Educacion-Ciencia [CVI 226, PC08-CTS-04046]
- ME-MICINN [SAF-2008-0368, SAF-2011-27261]
- JAE-Doc-CSIC-Contract
- Consejeria de Innovacion, Ciencia y Empresa, JA [P08-CTS-04046]
- [CSIC-PI-200820I216]
- [201420E095]
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Background MicroRNAs (miRNAs) gene expression regulators are altered in psoriasis suggesting their role in the pathogenesis. Objective To study expression changes of inflammation and toll-like receptor (TLR)-related miRNAs, miRNA-155, let-7i, miRNA-21, miRNA-146a and miRNA-223 in peripheral mononuclear cells (PBMCs) and miRNA-21, miRNA-146a and miRNA-223 in plasma, from chronic plaque-type psoriasis patients who were treatment-naive or had undergone a washout period (n = 11). MiRNAs were evaluated at baseline and after 11 (9-12) months [median (25th-75th percentile range)] of methotrexate (MTX) or topical (betamethasone plus calcipotriene) treatment. Methods MiRNA expression was analysed with quantitative real-time reverse transcription-polymerase chain reaction. Matched controls were studied. Results Psoriasis patients presented, at baseline, increased expression of miRNA-155, let-7i, miRNA-146a, miRNA-21 and miRNA-223 in PBMCs, plus miRNA-21, miRNA-146a and miRNA-223 in plasma. Receiver-operator characteristic (ROC) curve analysis and area under the curve (AUC) showed that expression of these miRNAs have the potential to distinguish between psoriasis and controls. At baseline, miRNA-155 expression in PBMCs correlated with Psoriasis Area Severity Index (PASI) [12 (8-14)] (Spearman r: 0.7140, P < 0.05) suggesting a role in psoriasis. After MTX or topical treatment, reduction in PASI was observed [87.5% (75-100)]; miRNA-155 expression in PBMCs decreased; plasma miRNA-21, miRNA-146a and miRNA-223 were down-regulated. ROC analysis showed that miRNA-155 expression in PBMCs from psoriasis patients have the potential to distinguish between patients' samples at baseline and after treatment (AUC: 0.942, sensitivity: 0.91; specificity: 0.91 values; maximum likelihood ratio = 10). After treatment, miRNA-146a expression in PBMCs increased; miRNA-155/miRNA-146a ratio decreased, suggestive of a regulatory feedback; let-7i expression decreased; miRNA-21 and miRNA-223 remained elevated. Conclusion In this exploratory study, psoriasis patients presented increased expression of miRNA-155 in PBMCs that correlated with PASI and decreased with disease remission. MiRNA-21, miRNA-146a and miRNA-223 in PBMCs and plasma were increased at baseline and differentially modulated, underscoring different roles of TLR-related miRNAs in psoriasis.
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