Urinary Exosomal miRNA Signature in Type II Diabetic Nephropathy Patients.
Urinary Exosomal miRNA Signature in Type II Diabetic Nephropathy Patients.
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DOI：
10.1371/journal.pone.0150154
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Urquhart R
中科院分区：
文献类型：
--
作者：
Delić D;Eisele C;Schmid R;Baum P;Wiech F;Gerl M;Zimdahl H;Pullen SS;Urquhart R
MicroRNA（miRNA）是短链非编码RNA，是基因表达的重要转录后调节因子，在糖尿病肾病的发病机制中发挥着重要作用。 miRNA 以非常稳定的形式存在于尿液中，包装在细胞外囊泡（主要是外泌体）中。在本研究中，使用安捷伦的 miRNA 微阵列对从 8 名健康对照者 (C)、8 名 II 型糖尿病患者 (T2D) 和 8 名 II 型糖尿病肾病 (DN) 患者获得的尿液外泌体进行了尿液外泌体 miRNA 分析。总体而言，与健康供体和 T2D 患者相比，DN 患者中 16 种 miRNA 的表达失调（>2 倍）：14 种 miRNA 的表达（miR-320c、miR-6068、miR-1234-5p、miR-6133、miR-4270、miR-4739、miR-371b-5p、miR-638、 miR-572、miR-1227-5p、miR-6126、miR-1915-5p、miR-4778-5p 和 miR-2861）上调，而 2 个 miRNA（miR-30d-5p 和 miR-30e-5p）的表达下调。大多数失调的 miRNA 与肾脏疾病的进展有关。尿外泌体 miRNA 的失调发生在微量白蛋白尿 DN 患者中，但在正常白蛋白尿 DN 患者中则没有。我们对 DN 患者尿液外泌体中上调最强烈的 miRNA（miRNA miR-320c 和 miR-6068）进行了基于 qRT-PCR 的分析。 miRNA 表达和微量白蛋白尿水平的相关性可以在确认队列中复制。总之，患有 DN 的 II 型糖尿病患者尿液外泌体 miRNA 含量发生改变。失调的 miR-320c 可能通过靶向血小板反应蛋白 1 (TSP-1) 对 TGF-β 信号通路产生影响，有望成为 II 型 DN 疾病进展的新型候选标志物，应在未来的研究中进行评估。
MicroRNAs (miRNAs) are short non-coding RNA species which are important post-transcriptional regulators of gene expression and play an important role in the pathogenesis of diabetic nephropathy. miRNAs are present in urine in a remarkably stable form packaged in extracellular vesicles, predominantly exosomes. In the present study, urinary exosomal miRNA profiling was conducted in urinary exosomes obtained from 8 healthy controls (C), 8 patients with type II diabetes (T2D) and 8 patients with type II diabetic nephropathy (DN) using Agilent´s miRNA microarrays. In total, the expression of 16 miRNA species was deregulated (>2-fold) in DN patients compared to healthy donors and T2D patients: the expression of 14 miRNAs (miR-320c, miR-6068, miR-1234-5p, miR-6133, miR-4270, miR-4739, miR-371b-5p, miR-638, miR-572, miR-1227-5p, miR-6126, miR-1915-5p, miR-4778-5p and miR-2861) was up-regulated whereas the expression of 2 miRNAs (miR-30d-5p and miR-30e-5p) was down-regulated. Most of the deregulated miRNAs are involved in progression of renal diseases. Deregulation of urinary exosomal miRNAs occurred in micro-albuminuric DN patients but not in normo-albuminuric DN patients. We used qRT-PCR based analysis of the most strongly up-regulated miRNAs in urinary exosomes from DN patients, miRNAs miR-320c and miR-6068. The correlation of miRNA expression and micro-albuminuria levels could be replicated in a confirmation cohort. In conclusion, urinary exosomal miRNA content is altered in type II diabetic patients with DN. Deregulated miR-320c, which might have an impact on the TGF-β-signaling pathway via targeting thrombospondin 1 (TSP-1) shows promise as a novel candidate marker for disease progression in type II DN that should be evaluated in future studies.