Activated platelets can deliver mRNA regulatory Ago2.microRNA complexes to endothelial cells via microparticles
Activated platelets can deliver mRNA regulatory Ago2.microRNA complexes to endothelial cells via microparticles
复制标题
DOI：
10.1182/blood-2013-03-492801
复制
发表时间：
2013-07-11
期刊：
影响因子：
20.3
通讯作者：
Provost, Patrick
中科院分区：
文献类型：
--
作者：
Laffont, Benoit;Corduan, Aurelie;Provost, Patrick
血小板在维持止血和血栓形成中起着至关重要的作用。激活后，血小板从亲本细胞中释放出含有生物活性蛋白和遗传物质的膜结合微粒（MPs），这些微粒可能被转移到循环系统的受体细胞中，并在受体细胞中发挥强大的生物效应。血小板已被证明含有丰富多样的微rna，而血小板衍生的MPs是循环中最丰富的微囊泡。在这里，我们证明了凝血酶激活的人血小板优先释放MPs中的miR-223含量。这些MPs可以被人脐静脉内皮细胞（HUVEC）内化，导致血小板来源的miR-223的积累。血小板MPs含有功能性Argonaute 2 （Ago2）。miR-223复合物能够调节受体HUVEC中报告基因的表达。此外，我们证明了血小板mp来源的miR-223在信使RNA和蛋白质水平上调控2种内源性内皮基因的作用。我们的结果支持血小板MPs可能作为功能性Ago2的细胞间载体的设想。microRNA复合物可能在内皮细胞和循环系统的其他受体细胞中发挥基因表达的异型调节。
Platelets play a crucial role in the maintenance of hemostasis, as well as in thrombosis. Upon activation, platelets release small membrane-bound microparticles (MPs) containing bioactive proteins and genetic materials from their parental cells that may be transferred to, and exert potent biological effects in, recipient cells of the circulatory system. Platelets have been shown to contain an abundant and diverse array of microRNAs, and platelet-derived MPs are the most abundant microvesicles in the circulation. Here we demonstrate that human platelets activated with thrombin preferentially release their miR-223 content in MPs. These MPs can be internalized by human umbilical vein endothelial cells (HUVEC), leading to the accumulation of platelet-derived miR-223. Platelet MPs contain functional Argonaute 2 (Ago2).miR-223 complexes that are capable of regulating expression of a reporter gene in recipient HUVEC. Moreover, we demonstrate a role for platelet MP-derived miR-223 in the regulation of 2 endogenous endothelial genes, both at the messenger RNA and protein levels. Our results support a scenario by which platelet MPs may act as intercellular carriers of functional Ago2.microRNA complexes that may exert heterotypic regulation of gene expression in endothelial cells, and possibly other recipient cells of the circulatory system.