Department of Aerospace Physiology, Air Force Medical University, Xi'an 710032, China.
Int J Mol Sci. 2023 Feb 1;24(3):2788. doi: 10.3390/ijms24032788.
Hypoxia impairs blood-brain barrier (BBB) structure and function, causing pathophysiological changes in the context of stroke and high-altitude brain edema. Brain microvascular endothelial cells (BMECs) are major structural and functional elements of the BBB, and their exact role in hypoxia remains unknown. Here, we first deciphered the molecular events that occur in BMECs under 24 h hypoxia by whole-transcriptome sequencing assay. We found that hypoxia inhibited BMEC cell cycle progression and proliferation and downregulated minichromosome maintenance complex component 2 () expression. overexpression attenuated the inhibition of cell cycle progression and proliferation caused by hypoxia. Then, we predicted the upstream miRNAs of MCM2 through TargetScan and miRanDa and selected miR-212-3p, whose expression was significantly increased under hypoxia. Moreover, the miR-212-3p inhibitor attenuated the inhibition of cell cycle progression and cell proliferation caused by hypoxia by regulating MCM2. Taken together, these results suggest that the miR-212-3p/MCM2 axis plays an important role in BMECs under hypoxia and provide a potential target for the treatment of BBB disorder-related cerebrovascular disease.
缺氧会损害血脑屏障（BBB）的结构和功能，导致中风和高原脑水肿情况下的病理生理变化。脑微血管内皮细胞（BMECs）是 BBB 的主要结构和功能元素，其在缺氧下的确切作用尚不清楚。在这里，我们首先通过全转录组测序分析揭示了缺氧 24 小时后 BMEC 中发生的分子事件。我们发现，缺氧抑制 BMEC 细胞周期进程和增殖，并下调微小染色体维持复合物成分 2（MCM2）的表达。MCM2 的过表达减弱了缺氧引起的细胞周期进程和增殖抑制。然后，我们通过 TargetScan 和 miRanDa 预测了 MCM2 的上游 miRNA，并选择了表达明显增加的 miR-212-3p。此外，miR-212-3p 抑制剂通过调节 MCM2 减弱了缺氧引起的细胞周期进程和细胞增殖抑制。综上所述，这些结果表明，miR-212-3p/MCM2 轴在缺氧下的 BMECs 中发挥重要作用，并为治疗与 BBB 紊乱相关的脑血管疾病提供了一个潜在的靶点。
