Department of Medicine, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Toxicol Sci. 2012 Oct;129(2):256-67. doi: 10.1093/toxsci/kfs210. Epub 2012 Jun 15.
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 AKI and may play a critical role in the pathogenesis of kidney injury and tissue repair process.
微小 RNA（miRNAs）是参与转录后基因沉默的内源性非编码 RNA 分子。通过对全球 miRNA 表达谱进行分析，我们发现，在缺血/再灌注（I/R）或庆大霉素给药引起的肾小管损伤后，大鼠肾脏中 miR-21、-155 和 18a 高度上调。miR-21 和 -155 在这两种肾损伤模型的血液和尿液上清液中也表现出表达模式下降。此外，与 25 名健康志愿者相比，临床诊断为急性肾损伤（AKI）的 22 名患者的尿液中 miR-21 水平升高了 1.2 倍（p < 0.05），AKI 患者的 miR-155 降低了 1.5 倍（p < 0.01）。我们使用相关关系算法识别了这 3 个 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凋亡或细胞增殖相关的基因。综上所述，这些结果表明，miR-21 和 -155 可能可作为 AKI 检测的转化生物标志物，并可能在肾损伤和组织修复过程的发病机制中发挥关键作用。
