title: Involvement of cyclooxygenase-2 in gastric mucosal hypertrophy in gastrin transgenic mice.
abstract: Gastrin promotes gastric mucosal growth, and hypergastrinemia induces gastric mucosal hypertrophy. Recently, it has been reported that gastrin induces cyclooxygenase-2 (COX-2) in human gastric and colorectal cancer cell lines. However, whether COX-2 is involved in gastrin-induced gastric mucosal growth in vivo is unknown. We investigated the role of COX-2 in gastrin-induced gastric mucosal hypertrophy using gastrin transgenic mice. Hypergastrinemic mice [mice with mutated gastrin under the control of the beta-actin promoter (ACT-GAS mice)] received the COX-2 inhibitor celecoxib (0, 200, or 500 mg/kg of diet) from 5 wk of age and were killed at 16 or 24 wk. Some ACT-GAS mice received celecoxib from 16 wk and were killed at 24 wk. Eighty-week-old ACT-GAS mice without celecoxib treatment were also examined. The thickness of the gastric mucosa, cell populations, COX-2 expression, and PGE(2) levels were evaluated. All ACT-GAS mice showed gastric mucosal hypertrophy, and four of six 80-wk-old ACT-GAS mice developed gastric cancer. COX-2 was expressed in interstitial cells of the hypertrophic gastric mucosa and gastric cancers. Moreover, PGE(2) levels in the gastric mucosa of ACT-GAS mice were significantly higher than those of normal mice. With treatment with celecoxib, PGE(2) levels, the gastric mucosal thickness, and the number of total gastric cells per gastric gland of ACT-GAS mice were significantly decreased. The decrease in gastric mucosal thickness was caused by a reduction of foveolar hyperplasia. The thickness of glandules and the number of Ki67-positive cells were not significantly changed. In conclusion, COX-2 contributes to gastrin-induced mucosal hypertrophy of the stomach.
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Shogoin-Kawara-cho 54, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kanda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Seno
authors.forename: Mayumi
authors.initials: M
authors.lastname: Kawada
authors.forename: Tateo
authors.initials: T
authors.lastname: Sawabu
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Uenoyoma
authors.forename: Toshio
authors.initials: T
authors.lastname: Nakajima
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Konda
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Fukui
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Chiba
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000502:physiology*; D015232:Dinoprostone / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005755:Gastrins / Q000097:blood / Q000235:genetics*; D015870:Gene Expression; D006984:Hypertrophy / Q000188:drug therapy / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D011720:Pyrazoles / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000378:metabolism; D013449:Sulfonamides / Q000627:therapeutic use
chemical_list: D005755:Gastrins; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D000068579:Celecoxib; D015232:Dinoprostone