MiR-411 suppressed vein wall fibrosis by downregulating MMP-2 via targeting HIF-1α
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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.
KeywordsMiR-411 Vein wall fibrosis Deep venous thrombosis MMP HIF
This study was supported by a grant from Science and Technology Bureau of Wenzhou (H-20160002).
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