Department of Neurology, Beijing Friendship Hospital, Capital Medical University, NO.95 YongAn Road, Xuanwu District, Beijing, 100050, China.
Arch Virol. 2013 Dec;158(12):2443-52. doi: 10.1007/s00705-013-1744-1. Epub 2013 Jun 13.
Human cytomegalovirus (HCMV) infection has been shown to contribute to vascular disease through the induction of angiogenesis. However, the role of microRNA in angiogenesis induced by HCMV infection remains unclear. The present study was thus designed to explore the potential effect of miR-199a-5p on angiogenesis and to investigate the underlying mechanism in endothelial cells. We found that HCMV infection of endothelial cells (ECs) enhanced expression of miR-199a-5p and reduced the SIRT1 protein level at 24 h postinfection (hpi). Transfection with miR-199a-5p mimics significantly suppressed SIRT1 protein expression and promoted cellular migration and tube formation induced by HCMV infection, which could be reversed by transfection with an miR-199a-5p inhibitor. Furthermore, pretreatment with resveratrol depressed motility and tube formation of HCMV-infected ECs, which could be reversed by SIRT1 siRNA. Finally, overexpression of miR-199a-5p decreased the level of eNOS modulated by SIRT1, an effect repressed by transfection with an miR-199a-5p inhibitor. In summary, HCMV infection of endothelial cells upregulates miR-199a-5p expression and enhances cell migration and tube formation through downregulation of SIRT1/eNOS by miR-199a-5p.
人巨细胞病毒（HCMV）感染已被证明通过诱导血管生成导致血管疾病。然而，HCMV 感染诱导的 microRNA 在血管生成中的作用尚不清楚。因此，本研究旨在探讨 miR-199a-5p 在血管生成中的潜在作用，并研究内皮细胞中潜在的作用机制。我们发现 HCMV 感染内皮细胞（ECs）可增强 miR-199a-5p 的表达并降低感染后 24 小时（hpi）的 SIRT1 蛋白水平。miR-199a-5p 模拟物的转染可显著抑制 SIRT1 蛋白表达，并促进 HCMV 感染诱导的细胞迁移和管状形成，而 miR-199a-5p 抑制剂的转染可逆转这种作用。此外，白藜芦醇预处理可抑制 HCMV 感染的 ECs 的迁移和管状形成，而 SIRT1 siRNA 可逆转这种作用。最后，miR-199a-5p 的过表达降低了 SIRT1 调节的 eNOS 水平，而 miR-199a-5p 抑制剂的转染可抑制这种作用。总之，HCMV 感染内皮细胞可上调 miR-199a-5p 的表达，并通过 miR-199a-5p 下调 SIRT1/eNOS 增强细胞迁移和管状形成。
