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MiR-199a-5p promotes migration and tube formation of human cytomegalovirus-infected endothelial cells through downregulation of SIRT1 and eNOS

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Abstract

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.

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Acknowledgments

We thank Department of Microbiology School of Medicine Shandong University for virus preparation.

This work was supported by Beijing Natural Science Foundation (nos. 7102040 and 7132060), National Natural Science Foundation of China (nos. 81041020, 81271311 and 81241039), Traditional Chinese Medicine, Beijing Technology Development Fund (no. SF-2007-III-22), Beijing Excellent Talent Foundation (NO. 20071-D0300100062), High-Level Technical Training Project Funding of Beijing Health System (2011-3-004) and Beijing City Staff to Go Abroad Preferential Funding Scheme.

The authors have declared that no competing interests exist.

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Authors and Affiliations

  1. Department of Neurology, Beijing Friendship Hospital, Capital Medical University, NO.95 YongAn Road, Xuanwu District, Beijing, 100050, China

    Shanchao Zhang, Lei Liu, Ruijin Wang, Houzhen Tuo, Yanjun Guo, Li Yi, Jiawei Wang & Dexin Wang

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  1. Shanchao Zhang
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Correspondence to Jiawei Wang or Dexin Wang.

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Zhang, S., Liu, L., Wang, R. et al. MiR-199a-5p promotes migration and tube formation of human cytomegalovirus-infected endothelial cells through downregulation of SIRT1 and eNOS. Arch Virol 158, 2443–2452 (2013). https://doi.org/10.1007/s00705-013-1744-1

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