Research Article Prostaglandin E 2 stimulates VEGF expression in primary rat gastric fi broblasts through EP4 receptors

Vascular endothelial growth factor (VEGF), a fun- damental regulator of angiogenesis, plays an important role in gastric ulcer healing. In addition, prostaglandin E2 (PGE2), derived from cyclooxygenase-2, stimulates VEGF release in gastric fi broblasts. In the present study, we examined which EP receptor subtype is involved in the expression of VEGF in primary rat gastric fi broblasts. PGE2 stimulated VEGF pro- tein expression in the fi broblasts in a time- and dose-depend- ent manner. The up-regulation by PGE2 of VEGF expression was completely inhibited by a subtype selective EP4 recep- tor antagonist (AE3-208). Furthermore, the selective EP4 re- ceptor agonist, AE1-329, promoted VEGF expression in the fi broblasts, and this effect was also totally antagonized by AE3-208. These results suggest that PGE2 stimulates VEGF expression in gastric fi bloblasts through the activation of EP4 receptors, and this effect may be involved in the healing promoting action of PGE2 on gastric ulcers.