DISTRIBUTION AND EXPRESSION OF PANCREATIC SECRETORY TRYPSIN-INHIBITORAND ITS POSSIBLE ROLE IN EPITHELIAL RESTITUTION

Pancreatic secretory trypsin inhibitor (PSTI) is a potent serine prote ase inhibitor that prevents excessive digestion of the gastrointestina l mucus but may also directly affect epithelial function. We therefore examined the distribution of PSTI in the human adult and fetus using immunohistochemistry and in situ hybridization and examined its effect s on cell proliferation and migration in vitro PSTI peptide and mRNA w ere found in the exocrine pancreas, mucus-producing cells of the norma l gastrointestinal tract, acinar component of the normal breast, and s urface epithelial cells at the edge of benign gastric ulcers. Peptide, but not message, was identified in the renal proximal tubule, Probabl y reflecting reabsorption of filtered peptide. Purified human PSTI did not affect proliferation of the human colonic cell line HT-29 but cau sed a threefold increase in the rate of migration in an in vitro wound ing model of restitution, This effect was inhibited by co-administerin g a PSTI-neutralizing antibody, a transforming growth factor-beta-neut ralizing antibody, or an epidermal growth factor receptor-blocking ant ibody, As PSTI is widely distributed in several human organ systems an d stimulates cell migration in vitro, we conclude that PSTI is likely to have additional roles to that of preserving the gastrointestinal mu cous layer front excessive digestion.