Microvesicle-mediated Transfer of MicroRNA-150 from Monocytes to Endothelial Cells Promotes Angiogenesis
Microvesicle-mediated Transfer of MicroRNA-150 from Monocytes to Endothelial Cells Promotes Angiogenesis
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微泡介导的 microRNA-150 从单核细胞转移到内皮细胞可促进血管生成。
DOI：
10.1074/jbc.m113.489302
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发表时间：
2013-08-09
影响因子：
4.8
通讯作者：
Zhang, Chen-Yu
中科院分区：
文献类型：
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作者：
Li, Jing;Zhang, Yujing;Zhang, Chen-Yu
我们小组及其他研究小组近期的研究表明，微小RNA（microRNAs）可通过微泡（MVs）主动分泌到细胞外环境中，并作为分泌性信号分子发挥作用，影响受体细胞的表型。在此，我们研究了单核细胞分泌的miR - 150在促进内皮细胞毛细血管形成以及增强血管生成中的作用。体外毛细血管形成和体内血管生成实验表明，单核细胞衍生的微泡具有很强的促血管生成活性。通过去除单核细胞微泡中的miR - 150，并增加通常含低水平miR - 150的细胞所衍生微泡中的miR - 150，我们进一步证明在这些实验中，miR - 150的含量是单核细胞微泡促血管生成活性的原因。以肿瘤移植小鼠和ob/ob小鼠为模型，我们发现对于癌症和糖尿病等疾病，miR - 150的分泌增加，这显著促进了血管生成。然而，通过微泡将抗miR - 150反义寡核苷酸递送至肿瘤移植小鼠和ob/ob小鼠体内，却强烈抑制了这两种小鼠的血管生成。我们的研究结果共同表明，通过微泡分泌miR - 150可在体外和体内促进血管生成，并且我们还提出了一种基于微小RNA的新型疾病治疗方法。
Recent studies by our group and others show that microRNAs can be actively secreted into the extracellular environment through microvesicles (MVs) and function as secretory signaling molecules that influence the recipient cell phenotypes. Here we investigate the role of monocyte-secreted miR-150 in promoting the capillary tube formation of endothelial cells and in enhancing angiogenesis. In vitro capillary tube formation and in vivo angiogenesis assays showed that monocyte-derived MVs have strong pro-angiogenic activities. By depleting miR-150 from monocytic MVs and increasing miR-150 in MVs derived from cells that normally contain low levels of miR-150, we further demonstrated that the miR-150 content accounted for the pro-angiogenic activity of monocytic MVs in these assays. Using tumor-implanted mice and ob/ob mice as models, we revealed that miR-150 secretion, which is increased for diseases such as cancers and diabetes, significantly promotes angiogenesis. The delivery of anti-miR-150 antisense oligonucleotides into tumor-implanted mice and ob/ob mice via MVs, however, strongly reduced angiogenesis in both types of mice. Our results collectively demonstrate that secretion of miR-150 via MVs can promote angiogenesis in vitro and in vivo, and we also present a novel microRNA-based therapeutic approach for disease treatment.