MicroRNA-493 regulates angiogenesis in a rat model of ischemic stroke by targeting MIF
MicroRNA-493 regulates angiogenesis in a rat model of ischemic stroke by targeting MIF
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MicroRNA-493 通过靶向 MIF 调节缺血性中风大鼠模型的血管生成
DOI：
10.1111/febs.13697
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发表时间：
2016-05-01
期刊：
影响因子：
5.4
通讯作者：
Hu, Bo
中科院分区：
文献类型：
--
作者：
Li, Qian;He, Quanwei;Hu, Bo
MicroRNA-493 (miR-493) 已知可抑制肿瘤转移和血管生成，并且其表达在中风患者中降低。在本研究中，我们研究了 miR-493 在调节中风后血管生成中的作用。我们发现，大脑中动脉闭塞 (MCAO) 大鼠的缺血边界区 (IBZ) 以及氧糖剥夺大鼠脑微血管内皮细胞 (RBMEC) 中 miR-493 的表达降低。通过侧脑室注射 antagomir-493（一种合成的 miR-493 抑制剂）下调 miR-493，增加 IBZ 毛细血管密度，减少局灶性梗死体积，并改善 MCAO 大鼠的神经功能缺损。有趣的是，MCAO 还增加了大鼠 IBZ 中巨噬细胞迁移抑制因子 (MIF) 的表达。在暴露于氧糖剥夺的 RBMEC 中，MIF 表达也增加。我们发现miR-493直接靶向MIF，并且通过敲低MIF减弱miR-493抑制血管生成的保护作用。然后可以通过施用重组 MIF 来挽救这种效应。我们的研究结果强调了 miR-493 在调节 MCAO 后血管生成中的重要性，并表明 miR-493 是治疗中风的潜在治疗靶点。
MicroRNA-493 (miR-493) is known to suppress tumour metastasis and angiogenesis and its expression is decreased in stroke patients. In the present study, we investigated a role for miR-493 in regulating post-stroke angiogenesis. We found decreased expression of miR-493 in the ischemic boundary zone (IBZ) of rats subjected to middle cerebral artery occlusion (MCAO), and in rat brain microvascular endothelial cells (RBMECs) exposed to oxygen glucose deprivation. Down-regulating miR-493 with a lateral ventricular injection of antagomir-493, a synthetic miR-493 inhibitor, increased capillary density in the IBZ, decreased focal infarct volume and ameliorated neurologic deficits in rats subjected to MCAO. Intriguingly, MCAO also increased the expression of macrophage migration inhibitory factor (MIF) in the IBZ of rats; MIF expression was also increased in RBMECs exposed to oxygen glucose deprivation. We found that miR-493 directly targeted MIF, and that the protective effect of miR-493 inhibition in angiogenesis was attenuated by knocking down MIF. This effect could then be rescued by administration of recombinant MIF. Our findings highlight the importance of miR-493 in regulating angiogenesis after MCAO, and indicate that miR-493 is a potential therapeutic target in the treatment of stroke.