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Reduced Shh expression in TFF2‐overexpressing lesions of the gastric fundus under hypochlorhydric conditions
Author(s) -
Minegishi Y,
Suzuki H,
Arakawa M,
Fukushima Y,
Masaoka T,
Ishikawa T,
Wright NA,
Hibi T
Publication year - 2007
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2221
Subject(s) - sonic hedgehog , parietal cell , biology , gastric mucosa , medicine , endocrinology , immunohistochemistry , foveolar cell , context (archaeology) , gastric acid , stomach , pathology , secretion , immunology , microbiology and biotechnology , signal transduction , paleontology
Expression of sonic hedgehog (Shh), a morphogen for the gastric fundic glands, is reduced in the atrophic mucosa that develops in association with Helicobacter pylori infection, resulting in impaired differentiation of the fundic gland cells, increased expression of trefoil factor family 2 (TFF2) and the formation of spasmolytic polypeptide (SP)‐expressing metaplasia (SPEM), a preneoplastic lesion. However, it is still unresolved whether H. pylori ‐induced inflammation and the resultant reduction in parietal cell number or reduced parietal cell function per se reduces Shh expression. The present study was designed to clarify the expression of Shh and TFF2 in the context of parietal cell dysfunction in the absence of inflammation, using histamine H 2 receptor‐knockout (H 2 R‐null) mice and an acid exposure model. Age‐matched H 2 R‐null mice and wild‐type (WT) mice were used. The expression of Shh and TFF2 mRNA was quantified by quantitative RT‐PCR. Immunohistochemistry was also performed to detect the expression of Shh, TFF2 and cell markers. To study the effects of acid exposure, HCl solution was administered to the animals. The H 2 R‐null mice exhibited higher gastric pH, increased TFF2 expression and reduced Shh expression. Impaired mucous neck‐to‐zymogenic cell differentiation was observed in the H 2 R‐null mice. Furthermore, Shh expression increased in the presence of gastric acid and showed a significant correlation with gastric surface pH. In conclusion, our results suggest that persistent parietal cell dysfunction alone (suppressed gastric acid secretion), in the absence of inflammation or parietal cell loss caused by H. pylori infection, may be sufficient to down‐regulate Shh expression in TFF2‐overexpressing preneoplastic 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. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.