Increased Hepatocyte Growth Factor Content in Rat Stomach during Omeprazole Treatment

Abstract

Background and Aims: 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. Conclusion: Omeprazole-induced acceleration of gastric mucosal healing may be mediated at least in part by the reduced degradation of HGF in the stomach.

Early gene expression of hepatocyte growth factor in mononuclear phagocytes of rat liver after administration of carbon tetrachloride

“… HGF gene expression in small (1–6) or large (7–12) MNP of normal (1, 7) and acutely injured liver isolated at 6 h (2, 8), 12 h (3, 9), 24 h (4, 10), 48 h (5, 11) or 72 h (6, 12) after the application of CCl 4 . Total RNA was extracted from freshly isolated MNP and analysed by Northern blotting.…”

“… Modulation of HGF gene expression in cultured large MNP of normal rat liver. Large MNP were cultured for 1 day and treated with TNF‐α 100‐U/ml (2), TNF‐α 1000‐U/ml (3), interferon‐α 1000‐U/ml (4), or interferon‐γ 1000‐U/ml (6). Lanes 1 and 5 controls.…”

“…In vivo it has been shown to exert various biological effects on a wide variety of cell types (4). After partial hepatectomy or acute liver injury HGF levels rise during liver regeneration and patients with acute liver failure also show increased serum levels of HGF (5–7) indicating a physiological role of HGF in restoring liver mass (hepatocyte recovery) after a major loss. However, HGF is not supposed to be the only growth factor that is involved in liver regeneration.…”

Pathophysiology of Gastric Ulcer Development and Healing: Molecular Mechanisms and Novel Therapeutic Options

“…Other reports have suggested that several growth factors are involved in the ulcer healing effects of PPIs. In this regard, Kinoshita et al (1998) observed that the gastric levels of HGF were enhanced by omeprazole in rats with indomethacin-induced gastric damage. Moreover, the expression of EGF was found to be increased in the gastric mucosa of mice with indomethacin-induced injury, and further enhanced by omeprazole (Banerjee et al, 2008).…”

Do We Need Gastric Acid?

“…Artificial ulcers generated in rats lead to the release of growth factors at the topical site of the mucosa. Several of the growth factors, such as the hepatocyte growth factor, are activated only in acidic milieu, and ulcer healing is paradoxically prolonged in the absence of acid in animal models [102]. …”