Increased hepatocyte growth factor content in rat stomach during omeprazole treatment.
OBJECTIVE
Hepatocyte growth factor (HGF) is a potent mitogen of gastric epithelial cells, and its production is stimulated during the healing of gastric mucosal lesions. In this study, the effect of a proton pump inhibitor, omeprazole, on the production and degradation of HGF in the stomach was examined to elucidate the mechanism of the omeprazole-induced acceleration of gastric mucosal healing.


METHODS
Indomethacin-induced gastric mucosal lesions were induced in rats with or without omeprazole pretreatment. HGF gene expression and the content of HGF was investigated in the rat stomach. HGF degradation by gastric juice was also tested.


RESULTS
In omeprazole-treated rats, the healing of gastric mucosal lesions was accelerated in comparison with those of untreated rats. Although omeprazole treatment did not enhance the indomethacin-induced increase in HGF gene expression, it significantly augmented the gastric HGF content. Furthermore, omeprazole increased the gastric content not only of the inactive but also of the active heterodimeric form of HGF, and this appeared to be due to the inhibition of the HGF degradation by gastric juice.


CONCLUSIONS
Omeprazole-induced acceleration of gastric mucosal healing may be mediated at least in part by the reduced degradation of HGF in the stomach.
Kinoshita
Y
Y
Department of Medicine, Kobe University School of Medicine, Japan.
Hassan
M S
MS
Kawamura
M
M
Matsushima
Y
Y
Okada
A
A
Maekawa
T
T
Fukui
H
H
Waki
S
S
Kishi
K
K
Chiba
T
T
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005744:Gastric Acid / Q000737:chemistry; D005745:Gastric Acidity Determination; D005750:Gastric Juice / Q000737:chemistry; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005765:Gastrointestinal Agents / Q000737:chemistry / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D005796:Genes / Q000235:genetics; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D006868:Hydrolysis / Q000187:drug effects; D007213:Indomethacin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D008297:Male; D009853:Omeprazole / Q000008:administration & dosage / Q000494:pharmacology*; D010434:Pepsin A / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000737:chemistry / Q000187:drug effects*; D013272:Stomach Diseases / Q000139:chemically induced / Q000188:drug therapy; D014945:Wound Healing / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D005765:Gastrointestinal Agents; D017228:Hepatocyte Growth Factor; D010434:Pepsin A; D009853:Omeprazole; D007213:Indomethacin