Role of cyclooxygenase 2 in hepatocyte growth factor-mediated gastric epithelial restitution.
Migration of epithelial cells (restitution) is an essential step in the repair of gastric mucosal lesions. Although a variety of growth factors are reported to facilitate gastric epithelial restitution, the intracellular mechanisms of this process are not fully understood. In this study we investigated the effects of hepatocyte growth factor (HGF) on restitution of normal rat gastric epithelial RGM-1 cell monolayers after injury and examined whether cyclooxygenase-2 (COX-2) is involved in HGF-mediated epithelial restitution. Restitution of RGM-1 monolayers was assessed using a round wound restitution model. Application of HGF (5 ng/ml) significantly facilitated the restitution of RGM-1 monolayers after artificial wounding. HGF also induced expression of COX-2 protein in RGM-1 cells, and wounding itself induced COX-2 expression in the cells located at the edge of the wound. Inhibition of COX-2 activity by NS-398, a specific COX-2 inhibitor, significantly delayed the HGF-mediated restitution. These results suggest the involvement of COX-2 in the action of HGF on gastric epithelial restitution.
Horie-Sakata
K
K
Second Department of Internal Medicine, Dokkyo University School of Medicine, Mibu, Tochigi, Japan.
Shimada
T
T
Hiraishi
H
H
Terano
A
A
D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology; D005753:Gastric Mucosa / Q000166:cytology* / Q000473:pathology; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D009578:Nitrobenzenes / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D013276:Stomach Ulcer / Q000473:pathology / Q000503:physiopathology*; D013449:Sulfonamides / Q000494:pharmacology
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D017228:Hepatocyte Growth Factor; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases