Downregulation of the Long Non-Coding RNA Meg3 Promotes Angiogenesis After Ischemic Brain Injury by Activating Notch Signaling.
Downregulation of the Long Non-Coding RNA Meg3 Promotes Angiogenesis After Ischemic Brain Injury by Activating Notch Signaling.
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长非编码 RNA Meg3 的下调通过激活 Notch 信号促进缺血性脑损伤后的血管生成
DOI：
10.1007/s12035-016-0270-z
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发表时间：
2017-12
影响因子：
5.1
通讯作者：
Deng ZF
中科院分区：
文献类型：
--
作者：
Liu J;Li Q;Zhang KS;Hu B;Niu X;Zhou SM;Li SG;Luo YP;Wang Y;Deng ZF
缺血性脑损伤后的血管生成有助于缺血区血液供应的恢复。改善血管生成的策略可能有助于卒中后功能的恢复。近年来的研究表明，长链非编码RNA的功能障碍与血管生成有关。我们以前曾报道过长链非编码RNA（lncRNA）在缺血性卒中中异常表达。然而，对长链非编码RNA及其在卒中后血管生成中的作用知之甚少。在本研究中，我们鉴定了大鼠lncRNA，Meg3，并发现缺血性中风后Meg3显著减少。缺血性卒中后Meg3的过表达抑制功能恢复并降低毛细血管密度。下调Meg3可改善缺血性卒中后的脑损伤并增加血管生成。Meg3的沉默导致促血管生成效应，其通过增加内皮细胞迁移、增殖、发芽和管形成来证明。从机制上讲，我们发现Meg3在体内和体外都负调控notch通路。在内皮细胞中抑制notch信号转导逆转了Meg3下调诱导的促血管生成作用。本研究揭示了Meg3在缺血性脑卒中中的作用，并阐明了其在缺血性脑卒中后血管新生中的作用机制。
Angiogenesis after ischemic brain injury contributes to the restoration of blood supply in the ischemic zone. Strategies to improve angiogenesis may facilitate the function recovery after stroke. Recent researches have demonstrated that dysfunction of long non-coding RNAs are associated with angiogenesis. We have previously reported that long non-coding RNAs (lncRNAs) are aberrantly expressed in ischemic stroke. However, little is known about long non-coding RNAs and theirs role in angiogenesis after stroke. In this study, we identified a rat lncRNAs, Meg3, and found that Meg3 was significantly decreased after ischemic stroke. Overexpression of Meg3 suppressed functional recovery and decreased capillary density after ischemic stroke. Downregulation of Meg3 ameliorated brain lesion and increased angiogenesis after ischemic stroke. Silencing of Meg3 resulted in a proangiogenic effect evidenced by increased endothelial cell migration, proliferation, sprouting, and tube formation. Mechanistically, we showed that Meg3 negatively regulated notch pathway both in vivo and in vitro. Inhibition of notch signaling in endothelial cells reversed the proangiogenic effect induced by Meg3 downregulation. This study revealed the function of Meg3 in ischemic stroke and elucidated its mechanism in angiogenesis after ischemic stroke.
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