Increased urinary exosomal microRNAs in children with idiopathic nephrotic syndrome
Increased urinary exosomal microRNAs in children with idiopathic nephrotic syndrome
复制标题
特发性肾病综合征儿童尿外泌体 microRNA 增加。
DOI：
10.1016/j.ebiom.2018.11.018
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发表时间：
2019-01-01
期刊：
影响因子：
11.1
通讯作者：
Zhang, Chunni
中科院分区：
文献类型：
--
作者：
Chen, Tingting;Wang, Cheng;Zhang, Chunni
背景资料：尿外泌体miRNAs作为肾脏疾病理想的非侵入性生物标志物的潜力越来越受到关注;然而，关于其对儿科肾病综合征（NS）的诊断能力知之甚少。本研究旨在探讨尿外泌体miRNAs在儿童特发性NS中的临床价值。方法：收集129例NS患儿和126例年龄/性别匹配的健康对照者的尿液样本。通过高通量Illumina合成测序（SBS）技术分析尿外泌体的miRNA谱，然后用定量逆转录聚合酶链反应（RTqPCR）试验进行验证，该试验分为两个独立的队列。结果：Illumina SBS鉴定了30种NS儿童与对照组相比尿外泌体miRNAs显著增加（>= 5倍，P <0.05）。选择15种miRNA用于进一步研究，其中5种（miR-194- 5 p、miR-146 b-5 p、miR-378 a-3 p、miR-23 b-3 p和miR-30 a-5 p）通过RT-qPCR证实在NS中显著且稳定地增加（>3倍，P < .01），并且在临床缓解期显著降低（P < .001）。此外，miR-194- 5 p和miR-23 b-3 p的浓度与尿蛋白含量显著正相关，并且在高尿蛋白组中显著高于低尿蛋白组（分别为P <0.001和P <0.01）。这些尿外泌体miRNAs可能是有前途的和非侵入性的潜在生物标志物候选诊断，监测和分层儿科NS。基金：国家自然科学基金;生命科学分析化学国家重点实验室基金;国家基础研究计划;江苏省医学青年人才基金。(c)2018作者由爱思唯尔公司出版
Background: Urinary exosomal miRNAs are gaining increasing attention for their potential as ideal non-invasive biomarkers for kidney diseases; however, little is known about their diagnostic ability for paediatric nephrotic syndrome (NS). This study explored the clinical value of urinary exosomal miRNAs for paediatric idiopathic NS.Methods: Urine samples were collected from 129 NS children and 126 age-/sex-matched healthy controls. The miRNA profile of urinary exosomes was analysed by high-throughput Illumina sequencing via synthesis (SBS) technology followed by verification with a quantitative reverse-transcription polymerase chain reaction (RTqPCR) assay arranged in two independent cohorts. Additionally, paired urine samples from 65 of these patients were collected before and after treatment.Findings: The Illumina SBS identified 30 markedly increased urinary exosomal miRNAs in NS children compared with controls (>= 5-fold, P < .05). Fifteen miRNAs were selected for further investigation, of which 5 (miR-194-5p, miR-146b-5p, miR-378a-3p, miR-23b-3p and miR-30a-5p) were verified by RT-qPCR to be significantly and steadily increased in NS (>3-fold, P < .01) and markedly reduced during the clinical remission period (P < .001). Moreover, the concentrations of miR-194-5p and miR-23b-3p were significantly positively correlated with the urine protein content and were markedly higher in the high urine protein group than in the low urine protein group (P < .001 and P < .01, respectively).Interpretations: We identified 5 altered urinary exosomal miRNAs in NS children with disease progression and treatment. These urinary exosomal miRNAs could be promising and non-invasive potential biomarker candidates for diagnosing, monitoring and stratifying paediatric NS.Fund: National Natural Science Foundation of China; Fund of State Key Laboratory of Analytical Chemistry for Life Science; National Basic Research Programme of China; Foundation of Jiangsu Provincial Medical Youth Talent. (c) 2018 The Authors. Published by Elsevier B.V.