Role of growth factors in gastroduodenal protection and healing of peptic ulcers.

Proliferation and growth of gastroduodenal mucosal cells represent important elements of mucosal defense and any alterations in the balance between cell proliferation and cell loss may lead to trophic changes in mucosa. Acute mucosal lesions induced by local irritants such as bile salts, ethanol, aspirin, or stress are accompanied by widespread damage of surface epithelium followed by almost immediate repair due to mucosal cell restitution, which is unrelated to cell proliferation but does depend on the intrinsic property of mucosal cells to cover superficial defects. Cytoprotection involves the protection of the regeneration zone and the maintenance of blood flow to the mucosa. Various factors that exhibit mucosal growth-promoting action include EGF, gastrin, growth hormone, and GH-releasing factor. These factors protect the mucosa against acute injury but the mechanism of this effect is not clear. These trophic agents, especially EGF, accelerate the healing of chronic gastroduodenal ulceration and may contribute to the healing effects of sucralfate or De-Nol. These effects of trophic substances are related to their stimulation of cell proliferation and DNA, RNA, and protein synthesis and can be reversed by the suppression of mucosal growth. Prostaglandins, especially their stable methylated analogs, display trophic effects on the gastric mucosa but neither gastroprotective nor ulcer healing actions of PG can be attributed to their trophic effect. With increasing attention being paid to mucosal growth and repair as components of mucosal defense, the emphasis of drug therapy of acute or chronic gastroduodenal lesions is likely to move toward strengthening mucosal defense rather than the inhibition of aggressive factors.