title: Involvement of cyclooxygenase-2 in proliferation and morphogenesis induced by transforming growth factor alpha in gastric epithelial cells.
abstract: Transforming growth factor alpha is one of the most potent growth factors for gastrointestinal epithelium. In this study, we examined the roles of cyclooxygenase-2 on proliferation and morphogenesis of RGM1 rat gastric epithelial cells after stimulation with transforming growth factor alpha in vitro, RGM1 cells increased expression of cyclooxygenase-2 messenger RNA 20-60 min after stimulation with transforming growth factor alpha. Transforming growth factor alpha stimulated [3H]thymidine incorporation and tubulogenesis of RGM1 cells in collagen matrix, both of which were significantly suppressed by treatment with a cyclooxygenase-2 specific inhibitor, NS-398 or cyclooxygenase-2 antisense oligonucleotide. Both of the treatment lowered prostanoid production by enzyme immunoassay. The transforming growth factor alpha-induced expression of cyclooxygenase-2 is followed by cell proliferation and development of tubular morphology of RGM1 gastric epithelial cells. Treatment with cyclooxygenase-2 inhibitor and cyclooxygenase-2 antisense oligonucleotide suppressed these responses induced by transforming growth factor alpha suggesting the involvement of cyclooxygenase-2 in proliferation and morphogenesis in gastric mucosal epithelium.
authors.affiliation: Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine Suita, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sawaoka
authors.forename: S
authors.initials: S
authors.lastname: Tsuji
authors.forename: M
authors.initials: M
authors.lastname: Tsujii
authors.forename: E S
authors.initials: ES
authors.lastname: Gunawan
authors.forename: N
authors.initials: N
authors.lastname: Kawai
authors.forename: Y
authors.initials: Y
authors.lastname: Sasaki
authors.forename: M
authors.initials: M
authors.lastname: Hori
authors.forename: S
authors.initials: S
authors.lastname: Kawano
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects* / Q000502:physiology*; D002460:Cell Line; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D015870:Gene Expression; D007527:Isoenzymes / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects; D009578:Nitrobenzenes / Q000494:pharmacology; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013449:Sulfonamides / Q000494:pharmacology; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D009578:Nitrobenzenes; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D013449:Sulfonamides; D016211:Transforming Growth Factor alpha; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D015121:6-Ketoprostaglandin F1 alpha; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases