ZNF580 mediates eNOS expression and endothelial cell migration/proliferation via the TGF-β1/ALK5/Smad2 pathway

ZNF580 is a novel C2H2 zinc-finger nuclear transcription factor with potential involvement in the transforming growth factor-beta 1 (TGF-beta 1) signal transduction pathway. Emerging evidence suggests that TGF-beta 1 can regulate endothelial nitric oxide synthase (eNOS) expression in endothelial cells. This study aimed to determine if ZNF580 mediated eNOS expression and participated in endothelial cell migration and proliferation via the TGF-beta 1/Smad2/ZNF580/eNOS signaling pathway. Overexpression/downexpression of ZNF580 in EAhy926 cells leads to the enhancement/decrease of eNOS expression. TGF-beta 1 downregulated both ZNF580 and eNOS at the mRNA and protein levels in concentration- and time-dependent manners. ZNF580 and eNOS downregulation induced by TGF-beta 1 was blocked by the specific TGF-beta 1 type I receptor ALK5 inhibitor, SB431542. Overexpression of ZNF580 attenuated TGF-beta 1-induced inhibition of EAhy926 cell growth and mobility, and vice versa. These results suggest that ZNF580 mediates eNOS expression and endothelial cell migration/proliferation via the TGF-beta 1/ALK5/Smad2 pathway, and thus plays a crucial role in vascular endothelial cells.