Omeprazole promotes gastric epithelial cell migration.
Proton pump inhibitors (PPIs) are effective at preventing non-steroidal anti-inflammatory drug (NSAID)-induced gastric ulcers. They are also superior to histamine H(2)-receptor antagonists and misoprostol in treating NSAID-induced gastric ulcer healing. This study explored whether omeprazole, a PPI, can modulate ulcer healing through epithelial cell proliferation and/or cell migration using a rat normal gastric epithelial cell line (RGM-1). Flow cytometry was used to determine cell proliferation and an artificial wound model was used to measure cell migration. Western blot analysis was performed to evaluate the possible mechanisms of action. Omeprazole treatment (10(-8), 10(-6) and 10(-4)M) for 12 and 24 h did not promote cell proliferation. However, similar doses of the drug (10(-6) and 10(-4)M) incubated for 24-48 h significantly promoted the basal cell migration of gastric epithelial cells. Further, the higher concentration of omeprazole (10(-4)M) reversed the inhibitory action of indometacin (10(-5)) on cell migration. Western blot results showed that omeprazole did not increase cyclooxygenase-2 expression and did not activate signal transduction pathways, including extracellular signal-regulated kinase (ERK1/ERK2), P38 mitogenic-activated protein kinase, and phosphatidyl inositol 3-kinase. The results suggest that omeprazole is beneficial in basal ulcer healing and it reversed the adverse action of indometacin on ulcer repair under acid-independent conditions. These actions are likely to be mediated through the promotion of gastric epithelial cell migration but not cell proliferation.
Ng
Ka-Man
KM
Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan.
Cho
Chi-Hin
CH
Chang
Full-Young
FY
Luo
Jiing-Chyuan
JC
Lin
Han-Chieh
HC
Lin
Hsiao-Yi
HY
Chi
Chin-Wen
CW
Lee
Shou-Dong
SD
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects*; D005753:Gastric Mucosa / Q000166:cytology; D009853:Omeprazole / Q000494:pharmacology*; D054328:Proton Pump Inhibitors; D051381:Rats
D000897:Anti-Ulcer Agents; D054328:Proton Pump Inhibitors; D009853:Omeprazole