| Budget Amount *help |
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
Gastric acid secretion is regulated through the surface receptors for hisitamine, gastrin, and acetylcholine on parietal cells of the gastric oxyntic mucosa. Ghreline, a novel growth hormone-releasing peptide, is considered as one of the stimulants of acid secretion by the gastric mucosa. In H2R-null mice, the effect of so-called receptor upregulation is excluded as a causative factor for the decrease in the antisecretory effect because the H2R deficiency is congenital. One of the study was designed to investigate the relation between acid secretion and ghreline expression, which is independent of histamine, by using H2R-null mice. The experiments showed that ghreline production and secretion in the gastric mucosa were enhanced in genetic H2R knockout mice, suggesting that ghreline can promote acid secretion under particular conditions of the absence of a hisitamine-dependent pathway for acid secretion.
Expression of the sonic hedgehog (Shh), a morphogen for the gastric fundic glands, i
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s reduced in the atrophic mucosa that develops in association with Helicobacter pylon infection, resulting impaired differentiation of the fundic gland cells, increased expression of trefoil factor family 2 (TEF2) and the formation of spasmotlytic polypeptide expressing metaplasia, a preneoplastic lesion. To study the effects of acid exposure, HCL solution was administered to the H2R-null mice. These mice exhibited higher gastric pH, increased TEF2 expression and reduced Shh expression. Our results suggest that persistent parietal cell dysfunction may be sufficient to down-regulate Shh expression in TEF-2 overexpressing preneoplatic lesions of the gastric fundus. Since exposure to acid restored fundic Shh expression, appropriate gastric acid secretion may play an important role in the morphogen dynamics involved in the maintenance of gastric fundic gland homeostasis. Our findings have revealed that down-regulation of Shh expression can be evoked not only by the parietal cell loss associated with H pylon infection, but also by parietal cell dysfunction in the absence of inflammation and/or parietal loss. Our results suggest the important role of optimal gastric acid secretion, an important parameter of gastric Shh expression and in gastric gland homeostasis. Less
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