Prostaglandin E₂ stimulates VEGF expression in primary rat gastric fibroblasts through EP4 receptors

Abstract.

Vascular endothelial growth factor (VEGF), a fundamental 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 fibroblasts. In the present study, we examined which EP receptor subtype is involved in the expression of VEGF in primary rat gastric firoblasts. PGE₂ stimulated VEGF protein expression in the fibroblasts in a time- and dose-dependent manner. The up-regulation by PGE₂ of VEGF expression was completely inhibited by a subtype selective EP4 receptor antagonist (AE3-208). Furthermore, the selective EP4 receptor agonist, AE1-329, promoted VEGF expression in the fibroblasts, and this effect was also totally antagonized by AE3-208. These results suggest that PGE₂ stimulates VEGF expression in gastric fibloblasts through the activation of EP4 receptors, and this effect may be involved in the healing promoting action of PGE₂ on gastric ulcers.