Involvement of cyclooxygenase-2 in proliferation and morphogenesis induced by transforming growth factor alpha in gastric epithelial cells.
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.
Sawaoka
H
H
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine Suita, Japan.
Tsuji
S
S
Tsujii
M
M
Gunawan
E S
ES
Kawai
N
N
Sasaki
Y
Y
Hori
M
M
Kawano
S
S
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*
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