{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,7,6]],"date-time":"2024-07-06T19:14:18Z","timestamp":1720293258380},"reference-count":39,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2006,6]]},"abstract":"<jats:p>We have previously shown heregulin (HRG)-\u03b1 expression in human gastric fibroblasts and its stimulation of gastric epithelial cell growth. Although cyclooxygenase (COX)-2 has also been shown to stimulate growth factor production in these cells, the interaction between COX-2 and HRG remains unknown. Conditioned media (CM) from gastric fibroblasts incubated with PGE<jats:sub>2<\/jats:sub>or interleukin (IL)-1\u03b2, a well known COX-2 inducer, were analyzed for their effect on erbB3 tyrosine phosphorylation in MKN28 gastric epithelial cells. HRG protein expression in fibroblast lysates and CM was also examined by western blot. HRG-\u03b1 and HRG-\u03b2 mRNA expression in gastric fibroblasts and human gastric tissue was examined by real-time quantitative PCR. HRG and COX-2 expressions in surgical resections of human gastric ulcer tissue were examined immunohistochemically. CM from fibroblasts incubated with PGE<jats:sub>2<\/jats:sub>, or IL-1\u03b2, stimulated erbB3 phosphorylation in MKN28 cells. Preincubation of the fibroblasts with celecoxib, a selective COX-2 inhibitor, suppressed CM-induced erbB3 phosphorylation. This inhibition was reversed by exogenous PGE<jats:sub>2<\/jats:sub>. As with erbB3 phophorylation, IL-1\u03b2 stimulated both HRG-\u03b1 and HRG-\u03b2 mRNA expression, as well as HRG release into gastric fibroblast CM. IL-1\u03b2-stimulated HRG expression and release were also inhibited by celecoxib, and exogenous PGE<jats:sub>2<\/jats:sub>restored this inhibitory effect, suggesting the activation of an IL-1\u03b2-COX-2-PGE<jats:sub>2<\/jats:sub>pathway that culminates in the release of HRG from fibroblasts. HRG-\u03b1 and HRG-\u03b2 mRNA levels were significantly higher in gastric ulcer tissue than in normal gastric mucosa. HRG immunoreactivity was found in interstitial cells of the gastric ulcer bed and coexpressed with COX-2. These results suggest that HRG might be a new member of the growth factor family involved in the COX-2-dependent ulcer repair process.<\/jats:p>","DOI":"10.1152\/ajpgi.00253.2005","type":"journal-article","created":{"date-parts":[[2005,12,16]],"date-time":"2005-12-16T01:25:56Z","timestamp":1134696356000},"page":"G1243-G1251","source":"Crossref","is-referenced-by-count":8,"title":["Heregulin-\u03b1 and heregulin-\u03b2 expression is linked to a COX-2-PGE<sub>2<\/sub>pathway in human gastric 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