miR-21 induces endothelial progenitor cells proliferation and angiogenesis via targeting FASLG and is a potential prognostic marker in deep venous thrombosis

作者：Xiaolong Du, Lei Hong, Lili Sun, Hongfei Sang, Aiming Qian, Wendong Li, Hao Zhuang, Huoqi Liang, Dandan Song, Chenglong Li, Wenbin Wang, Xiaoqiang Li · 发表于：Journal of Translational Medicine · 年份：2019 · DOI：10.1186/s12967-019-2015-z · 被引用次数：65 · 研究领域：Venous Thromboembolism Diagnosis and Management、Angiogenesis and VEGF in Cancer、Pulmonary Hypertension Research and Treatments

BACKGROUND: Deep venous thrombosis (DVT) of lower extremities is a common thrombotic disease, occurring either in isolation or as a complication of other diseases or procedures. MiR-21 is one of important microRNAs which play critical role in various cellular function. This study aim to determine the effect of miR-21 on endothelial progenitor cells (EPCs) and its role in predicting prognosis of DVT. METHODS: EPCs was isolated from DVT models and control subjects. miR-21 expression was confirmed by RT-PCR. Potential target mRNA was predicted by bioinformatics analysis. EPCs biological functions were examined by CCK-8 and tube formation assay. Besides, miR-21 expression was determined in DVT patients to investigate the correlation between miR-21 expression and prognosis of DVT. Cox proportional hazard regression analyses were also performed to reveal the risk factors associated with prognosis. RESULTS: Here, we found miR-21 was downregulated in EPCs of DVT model rats. Increased miR-21 expression promoted proliferation and angiogenesis of EPCs. Moreover, we demonstrated that FASLG was a target of miR-21 and revealed that FASLG knockdown inhibited function of EPCs. Upregulation of miR-21 led to thrombus resolution in a rat model of venous thrombosis. In addition, lower expression level of miR-21 in DVT patients was associated with an increase of recurrent DVT and post thrombotic syndrome (PTS). Furthermore, Cox proportional hazard regression analyses demonstrated miR-21 expressio...