Endothelial progenitor cells undergo an endothelial-to-mesenchymal transition-like process mediated by TGFβRI
Endothelial progenitor cells undergo an endothelial-to-mesenchymal transition-like process mediated by TGFβRI
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DOI：
10.1093/cvr/cvq236
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发表时间：
2010-12-01
影响因子：
10.8
通讯作者：
Peinado, Victor I.
中科院分区：
文献类型：
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作者：
Diez, Marta;Musri, Melina M.;Peinado, Victor I.
内皮祖细胞（EPC）已被证明可以修复肺内皮，尽管它们也可以迁移到动脉内膜并分化成平滑肌样（间充质）细胞，从而促进内膜增生。这一过程的分子机制尚未完全阐明。在此，我们研究了内皮细胞向间质细胞转化（EnMT）的基因是否有助于EPC间质细胞表型的获得，并评估了转化生长因子β 1（TGF β 1）是否与EPC间质细胞表型的获得有关。我们的研究结果表明，EPC与平滑肌细胞（SMC）共培养增加了间充质细胞标志物α-平滑肌肌动蛋白，sm 22-α，和心肌素，并降低内皮细胞标志物CD 31的表达。在相同的条件下，我们还观察到EnMT相关的转录因子：蛞蝓，蜗牛，zeb 1和内皮素-1的基因表达的伴随增加。这表明间充质表型的获得通过EnMT样过程发生。抑制TGF β受体I（TGF β RI）下调snail基因表达，阻断EnMT，促进EPC向内皮细胞系分化。此外，TGF β RI抑制剂可降低SMC刺激的EPC迁移，而不影响其功能和粘附能力。这些结果表明，EPC可能通过EnMT样过程分化为SMC样细胞，TGF β I在EPC的命运中起重要作用。
Endothelial progenitor cells (EPC) have been shown to repair pulmonary endothelium, although they can also migrate into the arterial intima and differentiate into smooth muscle-like (mesenchymal) cells contributing to intimal hyperplasia. The molecular mechanisms by which this process proceeds have not been fully elucidated. Here, we study whether genes involved in the endothelial-to-mesenchymal transition (EnMT) may contribute to the mesenchymal phenotype acquisition of EPC and we evaluate whether transforming growth factor beta 1 (TGF beta 1) is involved in this process.Our results show that co-culture of EPC with smooth muscle cells (SMC) increases the expression of the mesenchymal cell markers alpha-smooth muscle actin, sm22-alpha, and myocardin, and decreases the expression of the endothelial cell marker CD31. In the same conditions, we also observed a concomitant increase in the gene expression of the EnMT-related transcription factors: slug, snail, zeb1, and endothelin-1. This indicates that mesenchymal phenotype acquisition occurred through an EnMT-like process. Inhibition of TGF beta receptor I (TGF beta RI) downregulated snail gene expression, blocked the EnMT, and facilitated the differentiation of EPC to the endothelial cell lineage. Furthermore, TGF beta RI inhibition decreased migration of EPC stimulated by SMC without affecting their functionality and adhesion capacity.These results indicate that EPC may differentiate into SMC-like cells through an EnMT-like process and that TGF beta I plays an important role in the fate of EPC.