Snail is required for TGFβ-induced endothelial-mesenchymal transition of embryonic stem cell-derived endothelial cells

• Published in: Journal of cell science Vol. 121; no. 20; pp. 3317 - 3324
• Main Authors: Kokudo, Takashi, Suzuki, Yuka, Yoshimatsu, Yasuhiro, Yamazaki, Tomoko, Watabe, Tetsuro, Miyazono, Kohei
• Format: Journal Article
• Language: English
• Published: The Company of Biologists Limited 15.10.2008
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.028282

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 β (TGFβ). 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 TGFβ plays important roles during mural differentiation of mouse embryonic stem cell-derived endothelial cells (MESECs). TGFβ2 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 α-actin, SM22α and calponin, whereas a TGFβ type I receptor kinase inhibitor inhibited EndMT. Among the transcription factors involved in EMT, Snail was induced by TGFβ2 in MESECs. Tetracycline-regulated expression of Snail induced the differentiation of MESECs into mural cells, whereas knockdown of Snail expression abrogated TGFβ2-induced mural differentiation of MESECs. These results indicate that Snail mediates the actions of endogenous TGFβ signals that induce EndMT.