Cultured endothelial cells display endogenous activation of the canonical Wnt signaling pathway and express multiple ligands, receptors, and secreted modulators of Wnt signaling

被引:98
作者
Goodwin, Anne M.
Sullivan, Kaitlyn M.
D'Amore, Patricia A.
机构
[1] Schepens Eye Res Inst, Boston, MA 02114 USA
[2] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA
关键词
Wnt; angiogenesis; endothelial cells; beta-catenin; cell density;
D O I
10.1002/dvdy.20939
中图分类号
R602 [外科病理学、解剖学]; R32 [人体形态学];
学科分类号
100101 ;
摘要
A growing body of evidence implicates Writ signaling in the control of angiogenesis. To better understand the role of the Wnt/beta-catenin pathway in endothelial cells (EC), we examined endogenous signaling activity and signaling component expression in vascular cells. We observed stabilization of cytosolic beta-catenin and activation of a T-cell factor (TCF) -luciferase promoter, hallmarks of canonical Writ signaling activity, in cultured EC. This activity was increased in subconfluent EC, which are known to display characteristics of angiogenic EC, compared with confluent EC, which have a more differentiated phenotype. Endogenous TCF activity was inhibited by transfection with a secreted inhibitor of canonical Wnt signaling. A systematic analysis of Wnt, Fzd, SFRP, and Dkk gene expression in human EC (cultured and freshly isolated), smooth muscle cells (cultured), and aorta demonstrated that numerous Wnt signaling components are expressed by vascular cells. We conclude that Wnt signaling components are expressed and active in cultured EC.
引用
收藏
页码:3110 / 3120
页数:11
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