GASTRIC-MUCOSAL CELL-PROLIFERATION AND TGF-ALPHA IN THE HEALING OF PEPTIC-ULCERS IN HUMAN-SUBJECTS

We investigated the role of gastric mucosal proliferation and mucosal transforming growth factor-alpha (TGF alpha) in the healing of peptic ulcers in human subjects. During endoscopic observation, mucosal biops y specimens were taken from the ulcer margin for flow cytometric analy sis of the mucosal cell cycle and ELISA for mucosal TGF alpha content. Immunohistochemistry confirmed that biopsy specimens contained prolif erating gastric epithelial cells, TGF alpha, and the TGF alpha recepto r. When the stage of ulcer healing was categorized according to Sakita and Miwa, mucosal cell proliferation was less at active stages and gr adually increased during the healing process. The mucosal TGF alpha le vel at the ulcer margin was not detectable at the A(1) stage but incre ased to within the normal range during ulcer healing. After re-establi shment of the epithelial layer at the site of the ulcer, cell prolifer ation returned to normal and TGF alpha remained within the normal rang e. Immunohistochemistry showed coexistence of TGF alpha and its recept or within PCNA-positive proliferating cells. These results suggest tha t TGF alpha. and its receptor play an important role in gastric epithe lial cell replication. The increase in TGF alpha. at the ulcer margin might indicate a role in stimulation of gastric cell replication durin g ulcer healing.