HISTOCHEMICAL ANALYSIS OF HYPERPLASTIC STOMACH OF TGF-ALPHA TRANSGENIC MICE

Hypertrophic gastric mucosa in transgenic mice overexpressing transfor ming growth factor (TGF)-alpha showed mucosal cellular hyperplasia wit h dysplasia, suppression of gastric acid secretion, and chief and pari etal cell depletion. In order to clarify the effects of TGF-alpha on t he gastric mucose, we analyzed the stomach of TGF-alpha transgenic mic e by mucin histochemical staining and immunohistochemical analysis of TGF-alpha. In transgenic mice, especially those older than 3 months, t he fundic gland was notably atrophic but the total mucosa was thickene d. The mucous neck cells were hypersecretory and associated with abnor mal sulfation. Mucosal hyperplasia was caused by proliferation of surf ace epithelial cells, associated with formation of intracytoplasmic lu mina. The hyperplastic foveolar cells revealed production of a high am ount of sialomucin. In addition, the involved stomach regionally revea led collagenous fibrosis in the submucosal layer. The wide distributio n of TGF-alpha in the hyperplastic foveolar cells was in sharp contras t to negative expression in the foveolar cells in the control mice. Th ese findings demonstrated the various regulatory functions of TGF-alph a in mucin production, fibrogenesis, and neck cell proliferation in th e stomach.