Endothelial progenitor cells undergo an endothelial-to-mesenchymal transition-like process mediated by TGFβRI

  • Díez M
  • Musri M
  • Ferrer E
 et al. 
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Abstract

Time for primary review: 29 days Aims 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 hyper-plasia. 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 b1 (TGFb1) is involved in this process. Methods and results Our results show that co-culture of EPC with smooth muscle cells (SMC) increases the expression of the mesench-ymal cell markers a-smooth muscle actin, sm22-a, 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 TGFb receptor I (TGFbRI) downregulated snail gene expression, blocked the EnMT, and facilitated the differentiation of EPC to the endothelial cell lineage. Further-more, TGFbRI inhibition decreased migration of EPC stimulated by SMC without affecting their functionality and adhesion capacity. Conclusion These results indicate that EPC may differentiate into SMC-like cells through an EnMT-like process and that TGFbI plays an important role in the fate of EPC.

Author-supplied keywords

  • Endothelium repair
  • Migration
  • Smooth muscle cell differentiation
  • Stem cell
  • Vascular remodelling

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