Differential functions of genes regulated by VEGF-NFATc1 signaling pathway in the migration of pulmonary valve endothelial cells

作者：Jang Gun Hyuk; Park In Sook; Yang Jeong Hee; Bischoff Joyce; Lee You Mie^*

来源：FEBS Letters, 2010, 584(1): 141-146.

DOI：10.1016/j.febslet.2009.11.031

• Valve endothelial cells
• Nuclear factor in activated T cells c1
• Vascular endothelial growth factor
• Calcineurin
• Endothelial-mesenchymal
• transdifferentiation
• Down Syndrome critical region 1
• Heparin-binding EGF-like growth factor

We have reported that vascular endothelial growth factor (VEGF)-A induces the proliferation of human pulmonary valve endothelial cells (HPVECs) through nuclear factor in activated T cells (NFAT) c1 activation [1]. Here we show that VEGF-A increases the migration of HPVECs through NFATc1 activation, suggesting that VEGF-A/NFATc1 regulates the migration of HPVECs. To learn how this pathway may be involved in post-natal valvular repair, HPVECs were treated with VEGFA, with or without cyclosporine A to selectively block VEGF -NFATc1 signaling. Down Syndrome critical region 1 (DSCR1) and heparin-binding EGF-like growth factor (HB-EGF) are two genes identified by DNA microarray as being up-regulated by VEGF-A in a cyclosporine-A-sensitive manner. DSCR1 silencing increased the migration of ovine valve endothelial cells, whereas HB-EGF silencing inhibited migration. This differential effect suggests that VEGF-A/NFATc1 signaling might be a crucial coordinator of endothelial cell migration in post-natal valves.

• 出版日期2010-1-4