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Publication : Snail is required for TGFbeta-induced endothelial-mesenchymal transition of embryonic stem cell-derived endothelial cells.

First Author  Kokudo T Year  2008
Journal  J Cell Sci Volume  121
Issue  Pt 20 Pages  3317-24
PubMed ID  18796538 Mgi Jnum  J:142575
Mgi Id  MGI:3821786 Doi  10.1242/jcs.028282
Citation  Kokudo T, et al. (2008) Snail is required for TGFbeta-induced endothelial-mesenchymal transition of embryonic stem cell-derived endothelial cells. J Cell Sci 121(Pt 20):3317-24
abstractText  Epithelial-mesenchymal transition (EMT) plays important roles in various physiological and pathological processes, and is regulated by signaling pathways mediated by cytokines, including transforming growth factor beta (TGFbeta). Embryonic endothelial cells also undergo differentiation into mesenchymal cells during heart valve formation and aortic maturation. However, the molecular mechanisms that regulate such endothelial-mesenchymal transition (EndMT) remain to be elucidated. Here we show that TGFbeta plays important roles during mural differentiation of mouse embryonic stem cell-derived endothelial cells (MESECs). TGFbeta2 induced the differentiation of MESECs into mural cells, with a decrease in the expression of the endothelial marker claudin 5, and an increase in expression of the mural markers smooth muscle alpha-actin, SM22alpha and calponin, whereas a TGFbeta type I receptor kinase inhibitor inhibited EndMT. Among the transcription factors involved in EMT, Snail was induced by TGFbeta2 in MESECs. Tetracycline-regulated expression of Snail induced the differentiation of MESECs into mural cells, whereas knockdown of Snail expression abrogated TGFbeta2-induced mural differentiation of MESECs. These results indicate that Snail mediates the actions of endogenous TGFbeta signals that induce EndMT.
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