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

被引:254
作者
Kokudo, Takashi
Suzuki, Yuka
Yoshimatsu, Yasuhiro
Yamazaki, Tomoko
Watabe, Tetsuro [1 ]
Miyazono, Kohei
机构
[1] Univ Tokyo, Grad Sch Med, Dept Mol Pathol, Bunkyo Ku, Tokyo 1130033, Japan
关键词
TGF beta 2; T beta R-I inhibitor; Snail; EMT; EndMT; Embryonic stem cell; Claudin; 5; Smooth muscle alpha-actin;
D O I
10.1242/jcs.028282
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 (TGF beta). 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 TGF beta plays important roles during mural differentiation of mouse embryonic stem cell-derived endothelial cells ( MESECs). TGF beta 2 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, SM22 alpha and calponin, whereas a TGF beta type I receptor kinase inhibitor inhibited EndMT. Among the transcription factors involved in EMT, Snail was induced by TGF beta 2 in MESECs. Tetracycline-regulated expression of Snail induced the differentiation of MESECs into mural cells, whereas knockdown of Snail expression abrogated TGF beta 2-induced mural differentiation of MESECs. These results indicate that Snail mediates the actions of endogenous TGF beta signals that induce EndMT.
引用
收藏
页码:3317 / 3324
页数:8
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