Ramezani Ali, Devaney Joseph M, Cohen Scott, Wing Maria R, Scott Richard, Knoblach Susan, Singhal Rishi, Howard Lilian, Kopp Jeffrey B, Raj Dominic S
Division of Renal Diseases and Hypertension, The George Washington University School of Medicine, Washington, DC, USA.
Eur J Clin Invest. 2015 Apr;45(4):394-404. doi: 10.1111/eci.12420.
MicroRNAs (miRNAs) are noncoding RNA molecules that play important roles in the pathogenesis of various kidney diseases. We investigated whether patients with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) have distinct circulating and urinary miRNA expression profiles that could lead to potential development of noninvasive biomarkers of the disease.
Exosome miRNAs were extracted from plasma and urine samples of patients with primary FSGS (n = 16) or MCD (n = 5) and healthy controls (n = 5). Differences in miRNA abundance were examined using Affymetrix GeneChip miRNA 3.0 arrays. QRT-PCR was used to validate the findings from the array.
Comparison analysis of FSGS versus MCD revealed 126 and 155 differentially expressed miRNAs in plasma and in urine, respectively. Only 38 of these miRNAs were previously cited, whereas the remaining miRNAs have not been described. Comparison analysis showed that a significant number of miRNAs were downregulated in both plasma and urine samples of patients with FSGS compared to those with MCD. Plasma levels of miR-30b, miR-30c, miR-34b, miR-34c and miR-342 and urine levels of mir-1225-5p were upregulated in patients with MCD compared to patients with FSGS and controls (P < 0.001). Urinary levels of mir-1915 and miR-663 were downregulated in patients with FSGS compared to MCD and controls (P < 0.001), whereas the urinary levels of miR-155 were upregulated in patients with FSGS when compared to patients with MCD and controls (P < 0.005).
Patients with FSGS and MCD have a unique circulating and urinary miRNA profile. The diagnostic and prognostic potential of miRNAs in FSGS and MCD warrants further studies.
微小RNA(miRNA)是非编码RNA分子,在各种肾脏疾病的发病机制中起重要作用。我们研究了微小病变肾病(MCD)和局灶节段性肾小球硬化(FSGS)患者是否具有独特的循环和尿液miRNA表达谱,这可能导致该疾病无创生物标志物的潜在发展。
从原发性FSGS患者(n = 16)或MCD患者(n = 5)以及健康对照者(n = 5)的血浆和尿液样本中提取外泌体miRNA。使用Affymetrix GeneChip miRNA 3.0阵列检测miRNA丰度的差异。实时定量聚合酶链反应(QRT-PCR)用于验证阵列的结果。
FSGS与MCD的比较分析显示,血浆和尿液中分别有126个和155个差异表达的miRNA。这些miRNA中只有38个先前被引用过,而其余的miRNA尚未被描述。比较分析表明,与MCD患者相比,FSGS患者的血浆和尿液样本中大量miRNA表达下调。与FSGS患者和对照组相比,MCD患者血浆中miR-30b、miR-30c、miR-34b、miR-34c和miR-342水平以及尿液中mir-1225-5p水平上调(P < 0.001)。与MCD和对照组相比,FSGS患者尿液中mir-1915和miR-663水平下调(P < 0.001),而与MCD患者和对照组相比,FSGS患者尿液中miR-155水平上调(P < 0.005)。
FSGS和MCD患者具有独特的循环和尿液miRNA谱。miRNA在FSGS和MCD中的诊断和预后潜力值得进一步研究。