{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:18:35Z","timestamp":1790705915273,"version":"4.1.0"},"reference-count":49,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2007,10]]},"abstract":"\n We examined the involvement of cyclooxygenase (COX)-1 as well as COX-2 in the healing of gastric ulcers and investigated which prostaglandin (PG) EP receptor subtype is responsible for the healing-promoting action of PGE\n 2<\/jats:sub>\n . Male SD rats and C57BL\/6 mice, including wild-type, COX-1(\u2212\/\u2212), and COX-2(\u2212\/\u2212), were used. Gastric ulcers were produced by thermocauterization under ether anesthesia. Gastric ulcer healing was significantly delayed in both rats and mice by indomethacin and rofecoxib but not SC-560 given for 14 days after ulceration. The impaired healing was also observed in COX-2(\u2212\/\u2212) but not COX-1(\u2212\/\u2212) mice. Mucosal PGE\n 2<\/jats:sub>\n content increased after ulceration, and this response was significantly suppressed by indomethacin and rofecoxib but not SC-560. The delayed healing in mice caused by indomethacin was significantly reversed by the coadministration of 11-deoxy-PGE\n 1<\/jats:sub>\n (EP\n 3<\/jats:sub>\n \/EP\n 4<\/jats:sub>\n agonist) but not other prostanoids, including the EP\n 1<\/jats:sub>\n , EP\n 2<\/jats:sub>\n , and EP\n 3<\/jats:sub>\n agonists. By contrast, CJ-42794 (selective EP\n 4<\/jats:sub>\n antagonist) significantly delayed the ulcer healing in rats and mice. VEGF expression and angiogenesis were both upregulated in the ulcerated mucosa, and these responses were suppressed by indomethacin, rofocoxib, and CJ-42794. The expression of VEGF in primary rat gastric fibroblasts was increased by PGE\n 2<\/jats:sub>\n or AE1-329 (EP\n 4<\/jats:sub>\n agonist), and these responses were both attenuated by coadministration of CJ-42794. These results confirmed the importance of COX-2\/PGE\n 2<\/jats:sub>\n in the healing mechanism of gastric ulcers and further suggested that the healing-promoting action of PGE\n 2<\/jats:sub>\n is mediated by the activation of EP\n 4<\/jats:sub>\n receptors and is associated with VEGF expression.\n <\/jats:p>","DOI":"10.1152\/ajpgi.00131.2007","type":"journal-article","created":{"date-parts":[[2007,8,2]],"date-time":"2007-08-02T20:59:20Z","timestamp":1186088360000},"page":"G788-G797","source":"Crossref","is-referenced-by-count":57,"title":["Cyclooxygenase-2\/prostaglandin E\n 2<\/sub>\n accelerates the healing of gastric ulcers via EP\n 4<\/sub>\n 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