TGF-beta receptor kinase inhibitor enhances growth and integrity of embryonic stem cell-derived endothelial cells.

TGF-beta receptor kinase inhibitor enhances growth and integrity of embryonic stem cell-derived endothelial cells.
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DOI:
10.1083/jcb.200305147
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发表时间:
2003-12-22
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Miyazono K
Miyazono K
中科院分区:
其他
文献类型:
--
作者:
Watabe T;Nishihara A;Mishima K;Yamashita J;Shimizu K;Miyazawa K;Nishikawa S;Miyazono K

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最近的研究结果表明,胚胎血管祖细胞能够分化为壁细胞和内皮细胞。然而,调节其分化、增殖和内皮层形成的分子机制仍有待阐明。在这里,我们发现转化生长因子 (TGF)-β 超家族的成员在小鼠胚胎干细胞 (ESC) 和性交后 8.5 天胚胎来源的血管祖细胞的分化过程中发挥重要作用。 TGF-β和激活素抑制内皮细胞的增殖和片层形成。有趣的是,SB-431542(一种抑制 TGF-β 和激活素受体激酶的合成分子)可促进 ESC 衍生内皮细胞的增殖和片层形成。此外,SB-431542 上调claudin-5(紧密连接的内皮特异性成分)的表达。这些结果表明内源性TGF-β/激活素信号在调节血管生长和通透性中发挥重要作用。
Recent findings have shown that embryonic vascular progenitor cells are capable of differentiating into mural and endothelial cells. However, the molecular mechanisms that regulate their differentiation, proliferation, and endothelial sheet formation remain to be elucidated. Here, we show that members of the transforming growth factor (TGF)-β superfamily play important roles during differentiation of vascular progenitor cells derived from mouse embryonic stem cells (ESCs) and from 8.5–days postcoitum embryos. TGF-β and activin inhibited proliferation and sheet formation of endothelial cells. Interestingly, SB-431542, a synthetic molecule that inhibits the kinases of receptors for TGF-β and activin, facilitated proliferation and sheet formation of ESC-derived endothelial cells. Moreover, SB-431542 up-regulated the expression of claudin-5, an endothelial specific component of tight junctions. These results suggest that endogenous TGF-β/activin signals play important roles in regulating vascular growth and permeability.
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