Expression, Circulation, and Excretion Profile of MicroRNA-21,-155, and-18a Following Acute Kidney Injury
Expression, Circulation, and Excretion Profile of MicroRNA-21,-155, and-18a Following Acute Kidney Injury
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DOI：
10.1093/toxsci/kfs210
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发表时间：
2012-10-01
影响因子：
3.8
通讯作者：
Vaidya, Vishal S.
中科院分区：
文献类型：
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作者：
Saikumar, Janani;Hoffmann, Dana;Vaidya, Vishal S.
microRNA（miRNAs）是参与转录后基因沉默的内源性非编码RNA分子。使用全局miRNA表达谱，我们发现miR-21，-155和18 a在缺血/再灌注（I/R）或庆大霉素给药诱导的肾小管损伤后在大鼠肾脏中高度上调。在两种肾损伤模型中，Mir-21和-155在血液和尿液上清液中的表达模式也显示出降低。此外，与健康志愿者（n = 25）相比，临床诊断为急性肾损伤（阿基）的患者（n = 22）的尿液中miR-21水平增加了1.2倍（p < 0.05），而阿基患者的miR-155水平降低了1.5倍（p < 0.01）。我们使用相关性的上下文似然算法确定了这3种miRNA的29个信使RNA核心靶标，并发现这些预测的基因靶标高度富集与细胞凋亡或细胞增殖相关的基因。综上所述，这些结果表明，miRNA-21和-155可能作为检测AM的翻译生物标志物，并可能在肾损伤的发病机制和组织修复过程中发挥关键作用。
MicroRNAs (miRNAs) are endogenous noncoding RNA molecules that are involved in post-transcriptional gene silencing. Using global miRNA expression profiling, we found miR-21, -155, and 18a to be highly upregulated in rat kidneys following tubular injury induced by ischemia/reperfusion (I/R) or gentamicin administration. Mir-21 and -155 also showed decreased expression patterns in blood and urinary supernatants in both models of kidney injury. Furthermore, urinary levels of miR-21 increased 1.2-fold in patients with clinical diagnosis of acute kidney injury (AKI) (n = 22) as compared with healthy volunteers (n = 25) (p < 0.05), and miR-155 decreased 1.5-fold in patients with AKI (p < 0.01). We identified 29 messenger RNA core targets of these 3 miRNAs using the context likelihood of relatedness algorithm and found these predicted gene targets to be highly enriched for genes associated with apoptosis or cell proliferation. Taken together, these results suggest that miRNA-21 and -155 could potentially serve as translational biomarkers for detection of AM and may play a critical role in the pathogenesis of kidney injury and tissue repair process.