Small RNA-seq analysis of hypertensive patients with or without urinary albumin excretion

The goal of this study is to compare the plasma or exosomal (from urine and plasma) miRNA profiles of hypertensive patients with or without urinary albumin excretion. We analyzed 48 hypertensive subjects, 22 had elevated albuminuria and 26 were normoalbuminuric. Three individual small RNA libraries from each patient were prepared (total plasma, plasma exosomes and urine exosomes) for Next-Generation Sequencing (NGS) profiling. Differentially expressed circulating miRNAs were over-represented in KEGG pathways. Our results revealed a dysregulated exosomal miRNA signature associated to albuminuria in hypertension. The identified miRNAs are master regulators of key proteins in the maintenance of the glomerular filtration barrier, suggesting the potential use of exo-miRNAs as early biomarkers and therapeutic tools in kidney injury.

本研究旨在对比伴或不伴尿白蛋白排泄的高血压患者的血浆及（尿液、血浆来源的）外泌体（exosome）微小RNA（microRNA, miRNA）表达谱。本研究共纳入48名高血压受试者，其中22名存在白蛋白尿升高，26名为正常白蛋白尿。我们为每名受试者构建了3个独立的小RNA文库（总血浆、血浆来源外泌体及尿液来源外泌体），用于下一代测序（Next-Generation Sequencing, NGS）分析。差异表达的循环miRNA在京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）通路中显著富集。本研究结果揭示了高血压患者中与白蛋白尿相关的外泌体miRNA表达失调特征。所鉴定出的miRNA是维持肾小球滤过屏障关键蛋白的主要调控因子，这提示外泌体miRNA有望作为肾损伤早期生物标志物及治疗工具。