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 fibroblasts. 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 fibroblasts through the activation of EP4 receptors, and this effect may be involved in the healing promoting action of PGE2 on gastric ulcers.

Protective role of ascorbic acid isolated from Cissus quadrangularis on NSAID induced toxicity through immunomodulating response and growth factors expression

“…Prostaglandin, a key molecule that stimulates the complex array of ulcer healing mechanism, gets synthesized in the mucosal cells by cyclooxygenase (COX) enzymes [33]. The increase in PGE 2 may stimulate growth factors expression in gastric mucosa and this effect may be involved in the healing promoting action of PGE 2 on gastric ulcers which is consistent with the previous findings [34].…”

Prostaglandin E2Stimulates the Production of Vascular Endothelial Growth Factor through the E-Prostanoid–2 Receptor in Cultured Human Lung Fibroblasts

“…PGE 2 was reported to stimulate the release of VEGF in rat gastric fibroblasts through the EP4 receptor (21), and in human synovial fibroblasts through the EP2 and EP4 receptors (22). The present study extends these findings in several ways.…”

“…PGE 2 exerts its actions by acting on four distinct G protein-coupled E-prostanoid (EP) receptors that produce distinctly different effects (13)(14)(15)(16). The EP1 receptor regulates Ca 21 channel gating via an unidentified G protein. The EP2 and EP4 receptors couple to G s and mediate increases in concentrations of cAMP.…”

Direct Melanoma Cell Contact Induces Stromal Cell Autocrine Prostaglandin E2-EP4 Receptor Signaling That Drives Tumor Growth, Angiogenesis, and Metastasis

“…PGE 2 has been reported to induce the expression of VEGF in stromal fibroblasts, and EP2 and/or EP4 signaling is considered to be involved in the induction of VEGF (41,42). Using a gastric cancer mouse model, Guo et al (42) have reported that the PGE 2 and Wnt pathways play key roles in gastric tumorigenesis through the induction of VEGF production by stromal fibroblasts.…”