首页> 美国卫生研究院文献>International Journal of Clinical and Experimental Pathology >MiR-199a inhibits the angiogenic potential of endometrial stromal cells under hypoxia by targeting HIF-1α/VEGF pathway
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MiR-199a inhibits the angiogenic potential of endometrial stromal cells under hypoxia by targeting HIF-1α/VEGF pathway

机译:MiR-199a通过靶向HIF-1α/ VEGF途径抑制低氧条件下子宫内膜基质细胞的血管生成潜力

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摘要

We previously reported that miR-199a suppressed the invasiveness of endometrial stromal cells (ESCs) by targeting IkappaB kinase beta (IKKβ). This study was to investigate the role of miR-199a in the angiogenic potential of ESCs under hypoxia. Forced overexpression of miR-199a in ESCs significantly attenuated its angiogenic potential under hypoxia. Moreover, miR-199a down-regulated the expression level of vascular endothelial growth factor-A (VEGF-A) in ESCs under hypoxic conditions. To delineate the mechanism by which miR-199a reduced VEGF-A production, further analysis of the target genes of miR-199a showed that miR-199a targeted both VEGF-A and Hypoxia-inducible factor (HIF)-1α in ESCs. Our findings indicate that miR-199a may attenuate the angiogenic potential of ESCs under hypoxia partly through HIF-1α/VEGF-A pathway suppression. Therefore, miR-199a may play pivotal roles in the pathogenesis of endometriosis and may become a potential therapeutic target of this disease.
机译:我们先前曾报道miR-199a通过靶向IkappaB激酶beta(IKKβ)抑制子宫内膜间质细胞(ESCs)的侵袭性。这项研究旨在调查miR-199a在缺氧条件下的ESCs血管生成潜力中的作用。在缺氧条件下,miR-199a在ESC中的强迫过表达显着减弱了其血管生成潜力。此外,miR-199a在缺氧条件下下调了ESC中血管内皮生长因子-A(VEGF-A)的表达水平。为了描述miR-199a降低VEGF-A产生的机制,对miR-199a靶基因的进一步分析显示,miR-199a既靶向ESC中的VEGF-A又涉及缺氧诱导因子(HIF)-1α。我们的发现表明,miR-199a可能部分通过HIF-1α/ VEGF-A途径抑制而减弱缺氧条件下ESC的血管生成潜能。因此,miR-199a在子宫内膜异位症的发病机制中可能起关键作用,并可能成为该疾病的潜在治疗靶标。

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