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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-10-1
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-3417
pubmed:author
pubmed:issnType
Print
pubmed:volume
213
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
161-9
pubmed:meshHeading
pubmed-meshheading:17763396-Achlorhydria, pubmed-meshheading:17763396-Animals, pubmed-meshheading:17763396-Cell Differentiation, pubmed-meshheading:17763396-Down-Regulation, pubmed-meshheading:17763396-Gastric Acid, pubmed-meshheading:17763396-Gastric Fundus, pubmed-meshheading:17763396-Gene Expression Regulation, pubmed-meshheading:17763396-Hedgehog Proteins, pubmed-meshheading:17763396-Hydrochloric Acid, pubmed-meshheading:17763396-Hydrogen-Ion Concentration, pubmed-meshheading:17763396-Male, pubmed-meshheading:17763396-Mice, pubmed-meshheading:17763396-Mice, Knockout, pubmed-meshheading:17763396-Mucins, pubmed-meshheading:17763396-Muscle Proteins, pubmed-meshheading:17763396-Parietal Cells, Gastric, pubmed-meshheading:17763396-Peptides, pubmed-meshheading:17763396-RNA, Messenger, pubmed-meshheading:17763396-Receptors, Histamine H2, pubmed-meshheading:17763396-Reverse Transcriptase Polymerase Chain Reaction
pubmed:year
2007
pubmed:articleTitle
Reduced Shh expression in TFF2-overexpressing lesions of the gastric fundus under hypochlorhydric conditions.
pubmed:affiliation
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't