Retinoic Acid Stimulates the Dynamics of Mouse Gastric Epithelial Progenitors

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Abstract
The gastric epithelial progenitors proliferate and undergo bipolar migration associated with their differentiation into pit, parietal, and zymogenic cell lineages. Retinoids have long been known to modulate proliferation and differentiation of various renewing epithelia, and the expression of their receptors has been demonstrated in the gastric mucosa. The aim of this study was to examine the effects of retinoic acid on progenitor cell proliferation and cell lineage formation in the mouse stomach. By using subcutaneously inserted osmotic pumps, mice were continuously infused with all-trans retinoic acid (5 mg/kg per day) for 3 days. To label S-phase cells and their progeny, bromodeoxyuridine was administered for different time intervals. Analysis of gastric mucosal tissues of retinoic acid-treated mice revealed a significant increase in the number of S-phase progenitor cells and an enhancement in the production of their progeny. The life span of pit cells was reduced, and their apoptosis became apparent at the luminal surface. Immunofluoresence probing of pit, parietal and enteroendocrine cell lineages in control and retinoic acid-treated mice showed no significant change in their labeling pattern. However, there was an increase in the labeled gland area of zymogenic cells. In conclusion, 3-day treatment of retinoic acid enhances the proliferation of gastric epithelial progenitors and the dynamics of their progeny.