Endothelial progenitor cell-derived microvesicles activate an angiogenic program in endothelial cells by a horizontal transfer of mRNA
Endothelial progenitor cell-derived microvesicles activate an angiogenic program in endothelial cells by a horizontal transfer of mRNA
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DOI：
10.1182/blood-2007-03-078709
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发表时间：
2007-10-01
期刊：
影响因子：
20.3
通讯作者：
Camussi, Giovanni
中科院分区：
文献类型：
--
作者：
Deregibus, Maria Chiara;Cantaluppi, Vincenzo;Camussi, Giovanni
膜来源的微泡（MV）从细胞表面释放，并与细胞之间的通信有关。我们评估了从内皮祖细胞（EPC）得出的MV是否能够触发血管生成。我们发现，通过与Alpha A和在MV表面表达的β1整合素相互作用，将EPC衍生的MV掺入了内皮细胞中。在体外，MV促进了毛细血管样结构中的内皮细胞存活，增殖和组织。在体内，在严重的联合免疫缺陷（SCID）小鼠中，在专利血管中组织了MV刺激的人内皮细胞。当与RNase孵育时，尽管它们将其内部化为内皮细胞，但MV仍无法诱导体外和体内血管生成作用。通过含有GFP-MRNA的MVS在内皮细胞中的GFP蛋白转导和通过Lipofectamine递送的MV-MRNA提取物的血管生成作用的生物学相关性，显示了mRNA转移。 MV-MRNA提取物的微阵列分析和定量逆转录聚合酶链反应（RT-PCR）表明，MVS正在横穿特定的细胞mRNA子集，例如与PI3K/AKT信号通路相关的mRNA。蛋白质表达和功能研究表明，PI3K和ENOS在MV的血管生成作用中起关键作用。这些结果表明，EPC可以通过释放能够触发血管生成程序的MV来激活内皮细胞中的血管生成。
Membrane-derived microvesicles (MVs) are released from the cell surface and are implicated in cell-to-cell communication. We evaluated whether MVs derived from endothelial progenitor cells (EPCs) are able to trigger angiogenesis. We found that EPC-derived MVs were incorporated in endothelial cells by interaction with alpha A and beta 1 integrins expressed on the MV surface. In vitro, MVs promoted endothelial cell survival, proliferation, and organization in capillary-like structures. In vivo, in severe combined immunodeficient (SCID) mice, MV-stimulated human endothelial cells organized in patent vessels. When incubated with RNase, despite their internalization into endothelial cells, MVs failed to induce in vitro and in vivo angiogenic effects. mRNA transfer was shown by transduction of GFP protein in endothelial cells by MVs containing GFP-mRNA and the biologic relevance by the angiogenic effect of MV-mRNA extract delivered by lipofectamine. Microarray analysis and quantitative reverse transcription-polymerase chain reaction (RT-PCR) of MV-mRNA extract indicated that MVs were shuttling a specific subset of cellular mRNA, such as mRNA associated with the PI3K/AKT signaling pathway. Protein expression and functional studies showed that PI3K and eNOS play a critical role in the angiogenic effect of MVs. These results suggest that EPCs may activate angiogenesis in endothelial cells by releasing MVs able to trigger an angiogenic program.