miR-21 induces endothelial progenitor cells proliferation and angiogenesis via targeting FASLG and is a potential prognostic marker in deep venous thrombosis
miR-21 induces endothelial progenitor cells proliferation and angiogenesis via targeting FASLG and is a potential prognostic marker in deep venous thrombosis
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miR-21 通过靶向 FASLG 诱导内皮祖细胞增殖和血管生成，是深静脉血栓形成的潜在预后标志物
DOI：
10.1186/s12967-019-2015-z
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发表时间：
2019-08-15
影响因子：
7.4
通讯作者：
Li, Xiaoqiang
中科院分区：
文献类型：
--
作者：
Du, Xiaolong;Hong, Lei;Li, Xiaoqiang
研究背景下肢深静脉血栓形成(DVT)是一种常见的血栓性疾病，可单独发生，也可合并其他疾病或手术。MIR-21是重要的microRNAs之一，在多种细胞功能中发挥着重要作用。本研究旨在探讨miR-21对深静脉血栓内皮祖细胞的影响及其在预测深静脉血栓预后中的作用。RT-PCR检测到MIR-21的表达。通过生物信息学分析预测潜在的靶基因。用CCK-8法和小管形成实验检测EPC的生物学功能。此外，检测DVT患者的miR-21表达，探讨miR-21表达与DVT预后的关系。结果发现miR-21在DVT模型大鼠内皮祖细胞中表达下调。MiR-21表达增强促进内皮祖细胞增殖和血管生成。此外，我们还证明了FASLG是miR-21的靶点，并且发现FASLG基因敲除后抑制了内皮祖细胞的功能。在静脉血栓形成的大鼠模型中，miR-21上调导致血栓消退。另外，在DVT患者中miR-21表达水平降低与DVT复发和血栓形成后综合征(PTS)的增加有关。COX比例风险回归分析显示miR-21表达水平是DVT复发的独立预测因子。结论miR-21在EPC的生物学功能调节中发挥作用，可作为DVT或PTS复发的预测因子。
BackgroundDeep 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.MethodsEPCs 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.ResultsHere, 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 expression level as an independent predictor of recurrence of DVT.ConclusionsOur data revealed a role of miR-21 in regulating biological function of EPCs and could be a predictor for recurrent DVT or PTS.