Snail is required for TGFβ-induced endothelial-mesenchymal transition of embryonic stem cell-derived endothelial cells
Author:
Kokudo Takashi1, Suzuki Yuka1, Yoshimatsu Yasuhiro1, Yamazaki Tomoko1, Watabe Tetsuro1, Miyazono Kohei1
Affiliation:
1. Department of Molecular Pathology, Graduate School of Medicine and the Global Center of Excellence Program for `Integrative Life Science Based on the Study of Biosignaling Mechanisms', The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Abstract
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.
Publisher
The Company of Biologists
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