Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Colonic mucosal cells are known to contain several neuropeptides. The distribution of various peptide-containing cells in the colon and their possible modulation by aging and diet are unknown. We quantitated various peptide-containing cells from male Lobund-Wistar rat colon at 2, 22, 28, 30 and 33 months of age using indirect immunohistochemical techniques for several peptides including: neuropeptide Y, peptide YY, somatostatin, and chromogranin A. Four diets, varying in total calories and fat content, were examined. Serum gastrin was quantified by RIA at 2 and 33 months. Only NPY-, PYY- and SOM-positive cells were found in the colon. The number per crypt of neuropeptide Y-positive (0.55 +/- 0.04 at 2 months vs 0.80 +/- 0.22 at 33 months, P = 0.015) and peptide YY-positive cells increased with age. Staining for somatostatin and chromogranin, a marker for all enterochromaffin (EC) cells, revealed no change with aging. Diet did not influence the numbers of any peptide-containing cell. Serum gastrin was not different between the groups. A specific increase in NPY- and PYY-positive cells occurs in the aged rat colon. The extent to which this change may be related to age-related colonic dysmotility seen in elderly humans is worthy of exploration.
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PMID:Neuropeptide Y- and peptide YY-containing colonic cells increase with ageing in male rats. 891 66

The current study tests the hypothesis that chronic atrophic gastritis from hypochlorhydria in the gastrin-deficient mouse predisposes the stomach to gastric cancer. Gross morphology and histology of 12-month-old wild-type (WT), gastrin-deficient (G-/-) and somatostatin-deficient (SOM-/-) mice were examined. Parietal and G cells, Ki67, TUNEL, villin and MUC2 expression were analysed by immunohistochemistry. RUNX3 and STAT3 expression was analysed by Western blot. Anchorage-independent growth was determined by cell cluster formation in soft agar. Compared to the WT and SOM-/- mice, hypochlorhydric G-/- mice developed parietal cell atrophy, significant antral inflammation and intestinal metaplasia. Areas of metaplasia within the G-/- mouse stomach showed decreased RUNX3 expression with elevated MUC2 and villin expression. Cells isolated from the tumor grew in soft agar. However, the cells isolated from WT, nontransformed G-/- and SOM-/- gastric tissue did not form colonies in soft agar. Consistent with elevated antral proliferation, tumor tissue isolated from the G-/- mice showed elevated phosphorylated STAT3 expression. We then examined the mechanism by which STAT3 was constitutively expressed in the tumor tissue of the G-/- mice. We found that IFNgamma expression was also significantly higher in the tumor tissue of G-/- mice compared to WT and SOM-/- animals. To determine whether STAT3 was regulated by IFNgamma, MKN45 cells were cocultured with IFNgamma or gastrin. IFNgamma significantly stimulated phosphorylation of STAT3 in the MKN45 cell line, but not gastrin. Therefore, we show here that in the hypochlorhydric mouse stomach, the chronic gastritis, atrophy, metaplasia, dysplasia paradigm can be recapitulated in mice. Moreover, neoplastic transformation of the antral gastric mucosa does not require gastrin.
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PMID:Chronic gastritis in the hypochlorhydric gastrin-deficient mouse progresses to adenocarcinoma. 1573 48