Endogenous vascular endothelial growth factor-A (VEGF-A) maintains endothelial cell homeostasis by regulating VEGF receptor-2 transcription.

Publication Type:

Journal Article

Source:

The Journal of biological chemistry, Volume 287, Issue 5, p.3029-41 (2012)

Keywords:

Cells, Cultureddigestive disease, digestive deseases Endothelial Cellsdigestive disease, digestive deseases Forkhead Transcription Factorsdigestive disease, digestive deseases Gene Expression Regulationdigestive disease, digestive deseases Homeostasisdigestive disease, digestive deseases Humansdigestive disease, digestive deseases Response Elementsdigestive disease, digestive deseases Signal Transductiondigestive disease, digestive deseases Transcription, Geneticdigestive disease, digestive deseases Vascular Endothelial Growth Factor Adigestive disease, digestive deseases Vascular Endothelial Growth Factor Receptor-2digestive disease, digestive deseases Vesicular Transport Proteins

Abstract:

Vascular endothelial growth factor A (VEGF-A) is one of the most important factors controlling angiogenesis. Although the functions of exogenous VEGF-A have been widely studied, the roles of endogenous VEGF-A remain unclear. Here we focused on the mechanistic functions of endogenous VEGF-A in endothelial cells. We found that it is complexed with VEGF receptor 2 (VEGFR-2) and maintains a basal expression level for VEGFR-2 and its downstream signaling activation. Endogenous VEGF-A also controls expression of key endothelial specific genes including VEGFR-2, Tie-2, and vascular endothelial cadherin. Of importance, endogenous VEGF-A differs from exogenous VEGF-A by regulating VEGFR-2 transcription through mediation of FoxC2 binding to the FOX:ETS motif, and the complex formed by endogenous VEGF-A with VEGFR-2 is localized within the EEA1 (early endosome antigen 1) endosomal compartment. Taken together, our results emphasize the importance of endogenous VEGF-A in endothelial cells by regulating key vascular proteins and maintaining the endothelial homeostasis.