Upregulation of miR-483-3p contributes to endothelial progenitor cells dysfunction in deep vein thrombosis patients via SRF.

Lingshang Kong,Wenbin Wang,Wendong Li,Chenglong Li,Sen Wei,Xiaolong Du,Hong Chen,Nan Hu,Hao Zhuang,Xiaoqiang Li

doi:10.1186/s12967-016-0775-2

Abstract

BackgroundEndothelial progenitor cells (EPCs) contribute to recanalization of deep vein thrombosis (DVT). This study aimed to detect miRNA expression profiles in EPCs from patients with DVT and characterize the role of miRNA in EPCs dysfunction.MethodsEPCs was isolated from DVT patients and control subjects, and miRNA expression profiles were compared to screen differential miRNAs. The candidate miRNAs were confirmed by RT-PCR analysis. The targets of miRNA were identified by bioinformatics analyses, luciferase reporter assay and gene expression analyses. The apoptosis, migration and tube formation of EPCs were examined by flow cytometry, transwell assay and matrigel tube formation assay. A rat model of venous thrombosis was established as in vivo model.ResultsWe identified miR-483-3p as a candidate miRNA upregulated in EPCs from DVT patients. By using miR-483-3p agomir and antagomir, we demonstrated that miR-483-3p decreased the migration and tube formation while increased the apoptosis of EPCs. Moreover, we identified serum response factor (SRF) as the target of miR-483-3p, and showed that SRF knockdown decreased the migration and tube formation while increased the apoptosis of EPCs. In addition, miR-483-3p inhibition led to enhanced ability of homing and thrombus resolution of EPCs in rat model of venous thrombosis.ConclusionsmiR-483-3p is upregulated in EPCs from DVT patients, and it targets SRF to decrease EPCs migration and tube formation and increase apoptosis in vitro, while decrease EPCs homing and thrombus resolution in vivo. MiR-483-3p is a potential therapeutic target in DVT treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0775-2) contains supplementary material, which is available to authorized users.

Highlights

Endothelial progenitor cells (EPCs) contribute to recanalization of deep vein thrombosis (DVT)
The upregulation of miR‐483‐3p in EPCs from patients with DVT EPCs were isolated from both DVT patients (n = 3) and healthy donors (n = 3), and the expression of miRNA was determined using a microarray assay (Additional file 1: Figure S1)
Our results showed that the expression of miR-483-3p was significantly upregulated (Fig. 1, fivefold increase, P < 0.05), indicating the potential role of miR-483-3p in DVT

Summary

Introduction

Endothelial progenitor cells (EPCs) contribute to recanalization of deep vein thrombosis (DVT). Kong et al J Transl Med (2016) 14:23 recruited into the thrombus during a resolution and involved in thrombus recanalization [6,7,8]. Lower numbers of EPCs in the thrombus may result in diminished thrombus recanalization and resolution. MiRNAs participate in various biological events [9, 10], and recent studies suggested that miRNAs are involved in EPCs function [11]. MiR-130a was involved in the regulation of autophagy function in EPCs via targeting Runx3 [13]. Our previous studies showed that miR-150 and miR-126 contributed to EPCs function in vitro and improved thrombus recanalization and resolution in vivo [14, 15]

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