期刊
GUT
卷 62, 期 9, 页码 1270-1279出版社
BMJ PUBLISHING GROUP
DOI: 10.1136/gutjnl-2012-302401
关键词
CFTR; cholera; clusterin; cystic fibrosis; diarrhoeal disease; DMP-777; gastric cancer; gastrointestinal cancer; Helicobacter felis; H pylori-pathogenesis; molecular pathology; spasmolytic polypeptide-expressing metaplasia; stem cells; trefoil peptides
资金
- Department of Veterans Affairs
- NIH [RO1 DK071590, RO1 AI037750, P30 ES02109, R01 DK 077065, P50 CA95060]
- ARRA [DK071590-S1]
- Vanderbilt Digestive Disease Center [P30 DK058404]
- Vanderbilt-Ingram Cancer Center
Objectives Spasmolytic polypeptide-expressing metaplasia (SPEM) develops as a preneoplastic lesion in the stomachs of mice and humans after parietal cell loss. To identify the commonalities and differences between phenotypic SPEM lineages, SPEM were studied from three different mouse models of parietal cell loss: with chronic inflammation with Helicobacter felis infection; with acute inflammation with L635 treatment; and without inflammation following DMP-777 treatment. Design RNA transcripts from laser capture microdissected normal chief cells and SPEM lineages were compared using gene microarray. Alterations in transcripts were validated by quantitative real-time PCR. Clusterin and cystic fibrosis transmembrane conductance regulator (CFTR) were selected for immunohistochemical analysis in all mouse models as well as in human SPEM, intestinal metaplasia and gastric cancer. Results Transcript expression patterns demonstrated differences among the phenotypic SPEM models. Clusterin expression was significantly upregulated in all three mouse SPEM models as well as in human SPEM. The highest clusterin expression in human gastric cancers correlated with poor survival. Conversely, CFTR expression was upregulated only in SPEM with inflammation in mice. In humans, intestinal metaplasia, but not SPEM, expressed CFTR. Conclusions While markers such as clusterin are expressed in all phenotypic SPEM lineages, distinct patterns of upregulated genes including CFTR are present in murine metaplasia associated with inflammation, indicative of progression of metaplasia towards a more intestinalised metaplastic phenotype.
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