Downregulation of gastric mucin gene expression and its biosynthesis by dexamethasone in the human.

Abstract

The effect of corticosteroids on the release and biosynthesis of gastric mucin remains unclear. We studied the effects of dexamethasone on biosynthesis of mucin and MUC1 gene expression in the human stomach in vitro. Gastric mucosal specimens, obtained from six subjects at gastrectomy, were cultured with various concentrations of dexamethasone. Biosynthesis of mucin was studied by labeling gastric mucosa for 2 h with [3H]-glucosamine. After purification of mucin by CsCl gradient centrifugation, radioactivity of intra- and extracellular samples was counted. MUC1 gene expression was studied by Northern and dot-blot analysis using a cDNA encoding human gastric mucin gene MUC1. The dexamethasone treatment decreased mucin secretion from the isolated mucosa in a time- and concentration-dependent manner, with maximal inhibition of secretion (32+/-6%) observed after 8 h and 10(-5) M. Dexamethasone treatment also decreased MUC1 levels (28+/-9%). The inhibitory effect was also observed in carbachol-evoked secretion. These findings suggest that a decrease in mucin biosynthesis by corticosteroids may be involved in steroid-induced gastric mucosal damage.