Prostaglandin E2 stimulates VEGF expression in primary rat gastric fibroblasts through EP4 receptors.
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.
Hatazawa
R
R
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, Japan.
Tanigami
M
M
Izumi
N
N
Kamei
K
K
Tanaka
A
A
Takeuchi
K
K
D000818:Animals; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008738:Methyl Ethers / Q000494:pharmacology; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D051381:Rats; D018078:Receptors, Prostaglandin E / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D058309:Receptors, Prostaglandin E, EP4 Subtype; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D008738:Methyl Ethers; C461399:ONO-AE1-329; D011448:Prostaglandin Antagonists; C545652:Ptger4 protein, rat; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D015232:Dinoprostone