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Journal of Thrombosis and Thrombolysis

, Volume 45, Issue 2, pp 264–273 | Cite as

MiR-411 suppressed vein wall fibrosis by downregulating MMP-2 via targeting HIF-1α

  • Peng Ai
  • Bangli Shen
  • Hao Pan
  • Kui Chen
  • Jihang Zheng
  • Fengjun LiuEmail author
Article

Abstract

This study was aim to investigate the specific mechanisms of miR-411 in vein wall fibrosis remodeling. Vein wall fibrosis injury-induced deep venous thrombosis (DVT) rat model was well established. The expression of miR-411 at mRNA levels and Collagen I, hypoxia-inducible factor (HIF)-1α together with matrix metalloproteinase (MMP)-2 at protein levels in vein wall tissues and vascular smooth muscle cells (VSMCs) following transfection were determined using quantitative real-time PCR (qRT-PCR) and western blotting, respectively. Luciferase reporter assay was used to confirm the potential target of miR-411. MiR-411 mimic injected into rat model of DVT was to verify the role of miR-411 in vein wall fibrosis in vivo. MiR-411 was downregulated while Collagen I, HIF-1α and MMP-2 was upregulated in vein wall tissues and VSMCs obtained from rat model of DVT. MiR-411 overexpression in VSMCs separated from rats of vascular remodeling group (VR-VSMCs) upregulated miR-411, HIF-1α and inhibited cell proliferation and Collagen I expression, while miR-411 knockdown in VSMCs isolated from healthy rats (Control-VSMCs) reversed the effects. Furthermore, luciferase reporter assay demonstrated that HIF-1α was a target of miR-411. In addition, overexpression of miR-411 and HIF-1α in VR-VSMCs promoted HIF-1α, Collagen I expression and cell proliferation, however, tissue inhibitor of metalloproteinase (TIMP)-2 treatment led to adverse trends. MiR-411 mimic injected into rat model of DVT could suppress vein wall fibrosis in vivo. MiR-411 inhibited vein wall fibrosis by downregulating MMP-2 mediated by HIF-1α.

Keywords

MiR-411 Vein wall fibrosis Deep venous thrombosis MMP HIF 

Notes

Acknowledgements

This study was supported by a grant from Science and Technology Bureau of Wenzhou (H-20160002).

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  • Peng Ai
    • 1
  • Bangli Shen
    • 3
  • Hao Pan
    • 2
  • Kui Chen
    • 2
  • Jihang Zheng
    • 2
  • Fengjun Liu
    • 1
    Email author
  1. 1.Department of General SurgeryQilu Hospital of Shandong UniversityJinanChina
  2. 2.Department of Vascular SurgeryThe Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhouChina
  3. 3.Department of PainThe Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhouChina

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