{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T19:28:32Z","timestamp":1785094112267,"version":"3.55.0"},"reference-count":45,"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":[[2006,4]]},"abstract":"<jats:p> Traditional NSAIDs, selective cyclooxygenase (COX)-2 inhibitors, and inhibitors of nitric oxide synthase (NOS) impair the healing of preexisting gastric ulcers. However, the role of COX-1 (with or without impairment of COX-2) and the interaction between COX and NOS isoforms during healing are less clear. Thus we investigated healing and regulation of COX and NOS isoforms during ulcer healing in COX-1 and COX-2 deficiency and inhibition mouse models. In this study, female wild-type COX-1<jats:sup>\u2212\/\u2212<\/jats:sup> and COX-2<jats:sup>\u2212\/\u2212<\/jats:sup> mice with gastric ulcers induced by cryoprobe were treated intragastrically with vehicle, selective COX-1 (SC-560), COX-2 (celecoxib, rofecoxib, and valdedoxib), and unselective COX (piroxicam) inhibitors. Ulcer healing parameters, mRNA expression, and activity of COX and NOS were quantified. Gene disruption or inhibition of COX-1 did not impair ulcer healing. In contrast, COX-2 gene disruption and COX-2 inhibitors moderately impaired wound healing. More severe healing impairment was found in dual (SC-560 + rofecoxib) and unselective (piroxicam) COX inhibition and combined COX impairment (in COX-1<jats:sup>\u2212\/\u2212<\/jats:sup> mice with COX-2 inhibition and COX-2<jats:sup>\u2212\/\u2212<\/jats:sup> mice with COX-1 inhibition). In the ulcerated repair tissue, COX-2 mRNA in COX-1<jats:sup>\u2212\/\u2212<\/jats:sup> mice, COX-1 mRNA in COX-2<jats:sup>\u2212\/\u2212<\/jats:sup> mice, and, remarkably, NOS-2 and NOS-3 mRNA in COX-impaired mice were more upregulated than in wild-type mice. This study demonstrates that COX-2 is a key mediator in gastric wound healing. In contrast, COX-1 has no significant role in healing when COX-2 is unimpaired but becomes important when COX-2 is impaired. As counterregulatory mechanisms, mRNA of COX and NOS isoforms were increased during healing in COX-impaired mice. <\/jats:p>","DOI":"10.1152\/ajpgi.00416.2005","type":"journal-article","created":{"date-parts":[[2005,12,22]],"date-time":"2005-12-22T20:38:02Z","timestamp":1135283882000},"page":"G747-G756","source":"Crossref","is-referenced-by-count":33,"title":["Role of the different isoforms of cyclooxygenase and nitric oxide synthase during gastric ulcer healing in cyclooxygenase-1 and -2 knockout mice"],"prefix":"10.1152","volume":"290","author":[{"given":"Adrian","family":"Schmassmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Zoidl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitta M.","family":"Peskar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bea","family":"Waser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Schmassmann-Suhijar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan-Olaf","family":"Gebbers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Claude","family":"Reubi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2004.040238"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2036.2000.00836.x"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa050493"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1002\/jemt.1102"},{"key":"R5","unstructured":"Chan CC, Boyce S, Brideau C, Charleson S, Cromlish W, Ethier D, Evans J, Ford-Hutchinson AW, Forrest MJ, Gauthier JY, Gordon R, Gresser M, Guay J, Kargman S, Kennedy B, Leblanc Y, Leger S, Mancini J, O\u2019Neill GP, Ouellet M, Patrick D, Percival MD, Perrier H, Prasit P, Rodger I, Tagari P, Therien M, Vickers P, Visco D, Wang Z, Webb J, Wong E, Xu LJ, Young RN, Zamboni R, and Riendeau D. 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