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Cell lineage dynamics in the process leading to intestinal metaplasia.
MedLine Citation:
PMID:  21384254     Owner:  NLM     Status:  Publisher    
BACKGROUND: Gene expression in the early stage of the transition to intestinal metaplasia in human gastric mucosa has not been determined. In this study, we investigated the temporal relationship between cell lineage changes and intestine-specific gene expression in the process leading to intestinal metaplasia, using Cdx2-transgenic mice. METHODS: Cellular phenotypes were analyzed by immunohistochemistry and were compared with the gene expression profiles of cell lineage markers by real-time polymerase chain reaction. RESULTS: Up to postnatal day (PD) 20, the gastric mucosae of Cdx2-transgenic mice were histologically similar to those of their normal littermates. However, at approximately PD 20, we observed the sporadic appearance of glands in which all the epithelial cells expressed Cdx2 (Cdx2-diffuse positive glands). In the Cdx2-diffuse positive glands, parietal cells had disappeared, the proliferating zone had moved from the isthmus to the base, and absorptive cells and goblet cells were recognized. In contrast, the surrounding mucosa retained the phenotype of the gastric gland in which only some of the epithelial cells expressed Cdx2. During PDs 30 and 40, the entire fundic mucosa changed to transdifferentiated mucosa that was a composite of intestinal metaplasia and spasmolytic polypeptide-expressing metaplasia. An increase in the expression of intestine-specific genes, with a reciprocal decrease in gastric-specific gene expression, began much earlier than the emergence of Cdx2-diffuse positive glands. CONCLUSIONS: A dramatic increase in intestine-specific gene expression precedes the morphological appearance of intestinal metaplasia and spasmolytic polypeptide-expressing metaplasia.
Hirotsugu Sakamoto; Hiroyuki Mutoh; Hiroko Hayakawa; Miho Sashikawa; Kentaro Sugano
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-8
Journal Detail:
Title:  Journal of gastroenterology     Volume:  -     ISSN:  1435-5922     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-3-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9430794     Medline TA:  J Gastroenterol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Division of Gastroenterology, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan,
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