Zhang Shanchao, Liu Lei, Wang Ruijin, Tuo Houzhen, Guo Yanjun, Yi Li, Wang Dexin, Wang Jiawei
Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Xicheng District, Beijing, China.
PLoS One. 2013 Dec 20;8(12):e83620. doi: 10.1371/journal.pone.0083620. eCollection 2013.
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-1217 on angiogenesis and to disclose the underlying mechanism in endothelial cells. We found that HCMV infection of endothelial cells(ECs) enhanced expression of miR-217 and reduced SIRT1 and FOXO3A protein level in 24 hours post infection(hpi). Transfection of miR-217 inhibitor not only depressed cellular migration and tube formation induced by HCMV infection, but also enhanced SIRT1 and FOXO3A protein expression. Additionally, luciferase assay confirmed that miR-217 directly targeted FOXO3A mRNA 3`UTR. Furthermore, pretreatment with resveratrol depressed motility and tube formation of HCMV-infected ECs, which could be reversed by SIRT1 siRNA. Similarly, delivery of FOXO3A overexpression lentivirus suppressed proliferative rate, migration and tube formation of HCMV-infected ECs, which reversed by transfection of FOXO3A siRNA. In summary, HCMV infection of endothelial cells induces angiogenesis by both of miR-217/SIRT1 and miR-217/FOXO3A axis.
人巨细胞病毒（HCMV）感染已被证明可通过诱导血管生成促进血管疾病。然而，微小RNA在HCMV感染诱导的血管生成中的作用仍不清楚。因此，本研究旨在探讨miR-1217对血管生成的潜在影响，并揭示其在内皮细胞中的潜在机制。我们发现，内皮细胞（ECs）感染HCMV后，在感染后24小时（hpi）增强了miR-217的表达，并降低了SIRT1和FOXO3A蛋白水平。转染miR-217抑制剂不仅抑制了HCMV感染诱导的细胞迁移和管腔形成，还增强了SIRT1和FOXO3A蛋白表达。此外，荧光素酶测定证实miR-217直接靶向FOXO3A mRNA的3`UTR。此外，白藜芦醇预处理抑制了HCMV感染的ECs的运动性和管腔形成，而SIRT1 siRNA可逆转这种抑制作用。同样，递送FOXO3A过表达慢病毒抑制了HCMV感染的ECs的增殖率、迁移和管腔形成，而转染FOXO3A siRNA可逆转这种抑制作用。总之，内皮细胞感染HCMV通过miR-217/SIRT1和miR-217/FOXO3A轴诱导血管生成。
