Increased Urinary Exosomal MicroRNAs in Patients with Systemic Lupus Erythematosus.
Increased Urinary Exosomal MicroRNAs in Patients with Systemic Lupus Erythematosus.
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DOI：
10.1371/journal.pone.0138618
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Redon J
中科院分区：
文献类型：
--
作者：
Perez-Hernandez J;Forner MJ;Pinto C;Chaves FJ;Cortes R;Redon J
在不同疾病中使用microRNA（miRNAs）作为生物标志物的兴趣越来越大。存在于体液中，它们是否主要封闭在外泌体中是有争议的，因此我们研究了尿miRNA是否集中在外泌体中，以及是否存在系统性红斑狼疮伴或不伴狼疮性肾炎改变了它们的分布模式。我们通过定量逆转录PCR对系统性红斑狼疮患者（n = 38）和健康对照（n = 12）尿液中的特异性miRNA进行定量，包括无细胞尿液、外泌体去除上清液和通过超离心获得的外泌体沉淀。在对照组中，miR-335* 和miR-302 d在外泌体中始终高于外泌体去除的上清液，并且miR-200 c和miR-146 a在无细胞部分中更高。在狼疮患者中，测试的所有尿miRNA主要在外来体中，其外部水平较低（分别为p<0.05和p<0.01）。与对照组或没有狼疮肾炎的SLE患者相比，这种模式在活动性狼疮肾炎患者中尤其相关，其中miR-146 a增加最多（100倍变化，p<0.001）。在测试的外来体miRNA中，只有miR-146 a区分活动性狼疮肾炎的存在。总之，尿miRNAs主要包含在系统性红斑狼疮的外泌体中，并且在活动性狼疮肾炎的存在下发现主要增量。这些发现强调了尿液中外泌体miRNAs作为潜在肾脏疾病标志物的吸引力，这是一种非侵入性方法。
There is increased interest in using microRNAs (miRNAs) as biomarkers in different diseases. Present in body fluids, it is controversial whether or not they are mainly enclosed in exosomes, thus we studied if urinary miRNAs are concentrated inside exosomes and if the presence of systemic lupus erythematosus with or without lupus nephritis modifies their distribution pattern. We quantified specific miRNAs in urine of patients with systemic lupus erythematosus (n = 38) and healthy controls (n = 12) by quantitative reverse-transcription PCR in cell-free urine, exosome-depleted supernatant and exosome pellet obtained by ultracentrifugation. In control group, miR-335* and miR-302d were consistently higher in exosomes than in exosome-depleted supernatant, and miR-200c and miR-146a were higher in cell-free fraction. In lupus patients, all urinary miRNAs tested were mainly in exosomes with lower levels outside them (p<0.05 and p<0.01, respectively). This pattern is especially relevant in patients with active lupus nephritis compared to the control group or to the SLE patients in absence of lupus nephritis, with miR-146a being the most augmented (100-fold change, p<0.001). Among the exosomal miRNAs tested, only the miR-146a discriminates the presence of active lupus nephritis. In conclusion, urinary miRNAs are contained primarily in exosomes in systemic lupus erythematosus, and the main increment was found in the presence of active lupus nephritis. These findings underscore the attractiveness of exosomal miRNAs in urine, a non-invasive method, as potential renal disease markers.