Gastric epithelial cell proliferation after injury.

The mucosa of the gastrointestinal tract, including the stomach, undergoes constant renewal. The gastric mucosa is able to regenerate after injury, and this regeneration is associated with increases in epithelial cell proliferation. Gastric epithelial regeneration has been suggested to be impaired with aging. Using a hyperosmolar injury model, we found that gastric epithelial proliferation was markedly lower in aged rats. To elucidate further the regulation of gastric epithelial proliferation after injury, we studied the induction of ornithine decarboxylase and tyrosine kinase. Ornithine decarboxylase is the first and often rate-limiting enzyme in polyamine biosynthesis and tyrosine kinase catalyzes phosphorylation of protein tyrosine residues, and both enzymes have been implicated as important in cell proliferation. We found that hyperosmolar injury induction of ornithine decarboxylase and tyrosine kinase was markedly lower in aged rats. Furthermore, inhibition of ornithine decarboxylase or of tyrosine kinase greatly suppressed gastric epithelial proliferation. Our results confirm that ornithine decarboxylase and tyrosine kinase are important in gastric epithelial proliferation. Further studies of these two enzyme pathways may help elucidate the regulation of gastric epithelial growth and regeneration, particularly the potential alterations with aging.