Serum microRNA screening and functional studies reveal miR-483-5p as a potential driver of fibrosis in systemic sclerosis
Serum microRNA screening and functional studies reveal miR-483-5p as a potential driver of fibrosis in systemic sclerosis
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DOI：
10.1016/j.jaut.2017.12.015
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发表时间：
2018-05-01
影响因子：
12.8
通讯作者：
Radstake, Timothy R. D. J.
中科院分区：
文献类型：
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作者：
Chouri, Eleni;Servaas, Nila H.;Radstake, Timothy R. D. J.
目的：microRNAs(MiRNAs)是一种调节分子，被认为是风湿性疾病潜在的生物标志物和治疗靶点。在此，我们研究了系统性硬化症(SSC)患者血清中的miRNA特征，并进一步评估了其在疾病早期的表达情况。方法：采用Openarray平台检测26例SSC患者血清中758个miRNAs的水平，并与9名健康对照组进行比较。对107例SSC患者和24例健康献血员进行了3个miRNAs的单定量聚合酶链式反应(QPCR)检测。进一步分析了22例局限性硬皮病(LOS)、33例系统性红斑狼疮(SLE)和23例原发性干燥综合征(PSS)患者血清中MIR-483-5p的表达。将miR-483-5p导入原代培养的人真皮成纤维细胞和肺内皮细胞，检测miR-483-5p的功能。其中，miR-483-5p在独立的SSc队列中显示出可重复的较高水平，在有临床前SSc症状(早期SSc)的患者中也升高。值得注意的是，miR-483-5p在SLE和PSS患者中没有差异表达，而在LOS中表达上调，表明该miRNA可能参与了皮肤纤维化的发展。结论：从疾病早期起，miR-483-5p在SSC患者血清中表达上调，提示miR-483-5p可能作为SSC纤维化的精细调节因子。(C)2018年作者。爱思唯尔有限公司出版。
Objective: MicroRNAs (miRNAs) are regulatory molecules, which have been addressed as potential bio-markers and therapeutic targets in rheumatic diseases. Here, we investigated the miRNA signature in the serum of systemic sclerosis (SSc) patients and we further assessed their expression in early stages of the disease.Methods: The levels of 758 miRNAs were evaluated in the serum of 26 SSc patients as compared to 9 healthy controls by using an Openarray platform. Three miRNAs were examined in an additional cohort of 107 SSc patients and 24 healthy donors by single qPCR. MiR-483-5p expression was further analysed in the serum of patients with localized scleroderma (LoS) (n = 22), systemic lupus erythematosus (SLE) (n = 33) and primary Sjogren's syndrome (pSS) (n = 23). The function of miR-483-5p was examined by transfecting miR-483-5p into primary human dermal fibroblasts and pulmonary endothelial cells.Results: 30 miRNAs were significantly increased in patients with SSc. Of these, miR-483-5p showed reproducibly higher levels in an independent SSc cohort and was also elevated in patients with preclinical-SSc symptoms (early SSc). Notably, miR-483-5p was not differentially expressed in patients with SLE or pSS, whereas it was up-regulated in LoS, indicating that this miRNA could be involved in the development of skin fibrosis. Consistently, miR-483-5p overexpression in fibroblasts and endothelial cells modulated the expression of fibrosis-related genes.Conclusions: Our findings showed that miR-483-5p is up-regulated in the serum of SSc patients, from the early stages of the disease onwards, and indicated its potential function as a fine regulator of fibrosis in SSc. (C) 2018 The Authors. Published by Elsevier Ltd.