Histochemical analysis of hyperplastic stomach of TGF-alpha transgenic mice.

Hypertrophic gastric mucosa in transgenic mice overexpressing transforming growth factor (TGF)-alpha showed mucosal cellular hyperplasia with dysplasia, suppression of gastric acid secretion, and chief and parietal cell depletion. In order to clarify the effects of TGF-alpha on the gastric mucosa, we analyzed the stomach of TGF-alpha transgenic mice by mucin histochemical staining and immunohistochemical analysis of TGF-alpha. In transgenic mice, especially those older than 3 months, the fundic gland was notably atrophic but the total mucosa was thickened. The mucous neck cells were hypersecretory and associated with abnormal sulfation. Mucosal hyperplasia was caused by proliferation of surface epithelial cells, associated with formation of intracytoplasmic lumina. The hyperplastic foveolar cells revealed production of a high amount of sialomucin. In addition, the involved stomach regionally revealed collagenous fibrosis in the submucosal layer. The wide distribution of TGF-alpha in the hyperplastic foveolar cells was in sharp contrast to negative expression in the foveolar cells in the control mice. These findings demonstrated the various regulatory functions of TGF-alpha in mucin production, fibrogenesis, and neck cell proliferation in the stomach.