tRNA-Derived Small Non-Coding RNAs in Response to Ischemia Inhibit Angiogenesis.
tRNA-Derived Small Non-Coding RNAs in Response to Ischemia Inhibit Angiogenesis.
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tRNA 衍生的小非编码 RNA 响应缺血抑制血管生成
DOI：
10.1038/srep20850
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发表时间：
2016-02-11
影响因子：
4.6
通讯作者：
Deng ZF
中科院分区：
文献类型：
--
作者：
Li Q;Hu B;Hu GW;Chen CY;Niu X;Liu J;Zhou SM;Zhang CQ;Wang Y;Deng ZF
缺血性损伤会导致坏死组织损伤，而缺血后血管生成在血流恢复和组织恢复中起关键作用。最近，据报道有几种类型的小RNA参与了此过程。在这项研究中，我们首先生成了一个大鼠脑缺血模型，以研究新型小RNA在缺血中的参与。我们利用了深层测序和生物信息学分析，证明了缺血性大鼠脑中从TRNA中衍生出的小RNA片段的水平。在这些序列中，trnaval和trnagly衍生的小RNA是最丰富的段。通过北印迹和定量PCR分析，验证了trnaval和trnagly衍生片段的上调。在小鼠后肢缺血模型和细胞缺氧模型中，这两个片段的水平也增加了。重要的是，内皮细胞中trnaval和trnagly衍生的片段的上调抑制了细胞的增殖，迁移和管形成。此外，我们表明这些小的RNA是由血管葡萄蛋白裂解产生的。我们的结果表明，tRNA衍生的片段与组织缺血有关，我们首次证明trnaval-和trnagly衍生的片段通过调节内皮细胞的功能来抑制血管生成。
Ischemic injuries will lead to necrotic tissue damage and post-ischemia angiogenesis plays critical roles in blood flow restoration and tissue recovery. Recently, several types of small RNAs have been reported to be involved in this process. In this study, we first generated a rat brain ischemic model to investigate the involvement of new types of small RNAs in ischemia. We utilized deep sequencing and bioinformatics analyses to demonstrate that the level of small RNA fragments derived from tRNAs strikingly increased in the ischemic rat brain. Among these sequences, tRNAVal- and tRNAGly-derived small RNAs account for the most abundant segments. The up-regulation of tRNAVal- and tRNAGly-derived fragments was verified through northern blot and quantitative PCR analyses. The levels of these two fragments also increased in a mouse hindlimb ischemia model and cellular hypoxia model. Importantly, up-regulation of the tRNAVal- and tRNAGly-derived fragments in endothelial cells inhibited cell proliferation, migration and tube formation. Furthermore, we showed that these small RNAs are generated by angiogenin cleavage. Our results indicate that tRNA-derived fragments are involved in tissue ischemia and we demonstrate for the first time that tRNAVal- and tRNAGly-derived fragments inhibit angiogenesis by modulating the function of endothelial cells.