García-Rodríguez S, Arias-Santiago S, Blasco-Morente G, Orgaz-Molina J, Rosal-Vela A, Navarro P, Magro-Checa C, Martínez-López A, Ruiz J-C, Raya E, Naranjo-Sintes R, Sancho J, Zubiaur M
Department of Cellular Biology and Immunology, Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, Parque Tecnológico de la Salud de Granada (PTS Granada), Av. Conocimiento, 17, Granada-18016, Spain.
Department of Dermatology, Instituto de Investigación Biosanitaria de Granada, "ibs.GRANADA", Hospitales Universitarios de Granada (H. U. Granada)/Universidad de Granada (UGR), Granada, Spain.
J Eur Acad Dermatol Venereol. 2017 Feb;31(2):312-322. doi: 10.1111/jdv.13861. Epub 2016 Aug 17.
MicroRNAs (miRNAs) gene expression regulators are altered in psoriasis suggesting their role in the pathogenesis.
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.
MiRNA expression was analysed with quantitative real-time reverse transcription-polymerase chain reaction. Matched controls were studied.
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.
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.
微小RNA（miRNA）作为基因表达调节因子，在银屑病中发生改变，提示其在发病机制中发挥作用。
研究初治或经过洗脱期的慢性斑块型银屑病患者（n = 11）外周血单个核细胞（PBMC）中炎症及Toll样受体（TLR）相关miRNA，即miRNA-155、let-7i、miRNA-21、miRNA-146a和miRNA-223，以及血浆中miRNA-21、miRNA-146a和miRNA-223的表达变化。在甲氨蝶呤（MTX）或外用（倍他米松加卡泊三烯）治疗的基线期及11（9 - 12）个月[中位数（第25 - 75百分位数范围）]后对miRNA进行评估。
采用定量实时逆转录 - 聚合酶链反应分析miRNA表达。研究匹配的对照组。
银屑病患者在基线期时，PBMC中miRNA-155、let-7i、miRNA-146a、miRNA-21和miRNA-223表达增加，血浆中miRNA-21、miRNA-146a和miRNA-223表达也增加。受试者工作特征（ROC）曲线分析及曲线下面积（AUC）表明，这些miRNA的表达有区分银屑病患者与对照组的潜力。基线期时，PBMC中miRNA-155表达与银屑病面积和严重程度指数（PASI）[12（8 - 14）]相关（Spearman相关系数r：0.7140，P < 0.05），提示其在银屑病中发挥作用。MTX或外用治疗后，观察到PASI降低[87.5%（75 - 100）]；PBMC中miRNA-155表达降低；血浆中miRNA-21、miRNA-146a和miRNA-223下调。ROC分析表明，银屑病患者PBMC中miRNA-155表达有区分基线期和治疗后患者样本的潜力（AUC：0.942，敏感性：0.91；特异性：0.91；最大似然比 = 10）。治疗后，PBMC中miRNA-146a表达增加；miRNA-155/miRNA-146a比值降低，提示存在调节反馈；let-7i表达降低；miRNA-21和miRNA-223仍维持在较高水平。
在这项探索性研究中，银屑病患者PBMC中miRNA-155表达增加，与PASI相关且随疾病缓解而降低。PBMC和血浆中的miRNA-21、miRNA-146a和miRNA-223在基线期增加且受到不同调节，突出了TLR相关miRNA在银屑病中的不同作用。
