{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T04:31:32Z","timestamp":1762144292898},"reference-count":47,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2004,8]]},"abstract":"<jats:p>VEGF is a highly specific stimulator of endothelial cells and may play an important role in angiogenesis in the process of tissue regeneration. We previously showed that cyclooxygenase-2 (COX-2) expressed in mesenchymal cells of the ulcer bed is involved in the ulcer repair process. To clarify the role of COX-2 in angiogenesis during gastric ulcer healing, we investigated the relation between COX-2 expression and VEGF production in human gastric fibroblasts in vivo and in vitro. Gastric fibroblasts were cultured in RPMI 1640 with and without IL-1\u03b1 or IL-1\u03b2 in the presence or absence of NS-398, a selective COX-2 inhibitor. Supernatant VEGF and PGE<jats:sub>2<\/jats:sub>concentrations were measured by enzyme-linked immunosorbent assay. COX-2 expression in fibroblasts was determined by Western blot analysis. VEGF and COX-2 expression in surgical resections of human gastric ulcer tissue was examined immunohistochemically. IL-1 dose dependently enhanced VEGF release in cultured gastric fibroblasts after a 24-h stimulation. IL-1 also stimulated PGE<jats:sub>2<\/jats:sub>production in gastric fibroblasts via COX-2 induction. NS-398 significantly suppressed VEGF and PGE<jats:sub>2<\/jats:sub>release from IL-1-stimulated gastric fibroblasts; concurrent addition of PGE<jats:sub>2<\/jats:sub>restored NS-398-inhibited VEGF release. COX-2 and VEGF immunoreactivity were colocalized in fibroblast-like cells in the ulcer bed of gastric tissues. These results suggest that COX-2 plays a key role in VEGF production in gastric fibroblasts stimulated by IL-1 in vitro and that angiogenesis induced by the COX-2-VEGF pathway might be involved in gastric ulcer healing.<\/jats:p>","DOI":"10.1152\/ajpgi.00537.2003","type":"journal-article","created":{"date-parts":[[2004,7,10]],"date-time":"2004-07-10T01:44:10Z","timestamp":1089423850000},"page":"G444-G451","source":"Crossref","is-referenced-by-count":42,"title":["Cyclooxygenase-2-regulated vascular endothelial growth factor release in gastric 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