Differential functions of genes regulated by VEGF-NFATc1 signaling pathway in the migration of pulmonary valve endothelial cells.
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. 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 VEGF-A, 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.
Jang
Gun Hyuk
GH
School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea.
Park
In-Sook
IS
Yang
Jeong Hee
JH
Bischoff
Joyce
J
Lee
You Mie
YM
D000818:Animals; D002465:Cell Movement / Q000235:genetics*; D016572:Cyclosporine / Q000494:pharmacology; D004268:DNA-Binding Proteins; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D009124:Muscle Proteins / Q000235:genetics; D050778:NFATC Transcription Factors / Q000378:metabolism*; D011664:Pulmonary Valve / Q000166:cytology / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D050778:NFATC Transcription Factors; C494003:NFATC1 protein, human; C108612:RCAN1 protein, human; D042461:Vascular Endothelial Growth Factor A; D016572:Cyclosporine