STIMULATORY EFFECT OF TRANSFORMING GROWTH-FACTOR-ALPHA ON GASTRIC EPITHELIAL-CELL MIGRATION THROUGH PROLIFERATION

Transforming growth factor-alpha (TGF alpha) is a polypeptide that sti mulates gastric epithelial cell proliferation and inhibits gastric aci d secretion. Effects of TGF alpha are mediated by the epidermal growth factor receptor (EGFR). A recent study has shown the importance of TG F alpha in repairing gastric mucosa. Mucosal repair requires both prol iferation and migration of a variety of cells, dependent on the depth of injury. We studied the effect of TGF alpha on cell migration and pr oliferation using well-established rabbit gastric epithelial monolayer ed cells. TGF alpha enhanced cell migration at 24 h or later. However, TGF alpha had already stimulated tritiated thymidine (H-3-TdR) incorp oration into DNA of gastric epithelial cells at 18 h, suggesting that the promotional effect of TGF alpha on cell migration is a result of s timulated cell proliferation. In addition, coincubation of TGF alpha w ith hydroxyurea, which inhibits DNA synthesis, abolished the promotion al effect of TGF alpha on cell migration. These results indicate that TGF alpha's promotional effect on cell migration is secondary to its s timulatory effect on cell proliferation.