MicroRNAs Induced During Ischemic Preconditioning
MicroRNAs Induced During Ischemic Preconditioning
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DOI：
10.1161/strokeaha.110.579649
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发表时间：
2010-08-01
期刊：
影响因子：
8.3
通讯作者：
Roh, Jae-Kyu
中科院分区：
文献类型：
--
作者：
Lee, Soon-Tae;Chu, Kon;Roh, Jae-Kyu
背景和目的 - 微虫（miRNA）是单链的短RNA分子，通过降解或转化mRNA调节基因表达。尽管miRNA控制了许多疾病和疾病，但很少描述过神经保护miRNA。在这项研究中，我们研究了在缺血性预处理早期诱导的神经保护性miRNA。通过短暂闭塞脑中大脑动脉15或120分钟，诱导了小鼠 - 缺血性预处理或局灶性脑缺血。我们在缺血发作后3或24小时从缺血性皮层制备了RNA样品。然后将选择性miRNA合成并在氧葡萄糖剥夺之前将其转染到神经2a细胞中。回测 - 我们检测到总共360个miRNA。缺血性预处理后3小时，有选择性上调了两个miRNA家族，即miR-200和miR-182。其中一些的转染在体外缺血中是神经保护作用。其中，miR-200b，miR-200c和miR-429靶向丙酰羟化酶2，具有最佳的神经保护作用。结论两个miRNA家族，miR-200和miR-182在缺血性预处理后早期上调，而miR-- 200家族主要是通过下调羟基羟化酶2水平来受到神经保护的。这些miRNA在未来的研究和治疗应用中可能很有用。 （Stroke。2010; 41：1646-1651。）
Background and Purpose-MicroRNAs (miRNA) are single-stranded short RNA molecules that regulate gene expression by either degradation or translational repression of mRNA. Although miRNAs control a number of conditions and diseases, few neuroprotective miRNAs have been described. In this study, we investigated neuroprotective miRNAs induced early in ischemic preconditioning.Methods-Ischemic preconditioning or focal cerebral ischemia was induced in mice by transient occlusion of the middle cerebral artery for 15 or 120 minutes. We prepared RNA samples from the ischemic cortex at 3 or 24 hours after the onset of ischemia. Selective miRNAs then were synthesized and transfected into Neuro-2a cells before oxygen-glucose deprivation.Results-We detected a total of 360 miRNAs. Two miRNA families, miR-200 and miR-182, were selectively upregulated at 3 hours after ischemic preconditioning. Transfections of some of these were neuroprotective in in vitro ischemia. Among them, miR-200b, miR-200c, and miR-429 targeted prolyl hydroxylase 2 and had the best neuroprotective effect.Conclusion-Two miRNA families, miR-200 and miR-182, were upregulated early after ischemic preconditioning and the miR-200 family was neuroprotective mainly by downregulating prolyl hydroxylase 2 levels. These miRNAs may be useful in future research and therapeutic applications. (Stroke. 2010;41:1646-1651.)