Antacid talcid activates in gastric mucosa genes encoding for EGF and its receptor. The molecular basis for its ulcer healing action

In previous studies [Gut 35 (1994) 896-904], we demonstrated that antacid t alcid (TAL) accelerates gastric ulcer healing and provides better quality o f mucosal restoration within the scar than the omeprazole (OME). However, t he mechanisms of TAL-induced nicer healing are not clear. Since growth fact ors promote cell proliferation, re-epithelization, angiogenesis and ulcer h ealing, we studied whether TAL and/or OME affect expression of epidermal gr owth factor (EGF) and its receptors (EGF-R) in both normal and ulcerated ga stric mucosae. Rats with or without acetic acid-induced gastric ulcers (n = 64) received i.g. twice daily 1 mt of either: A) placebo (PLA); B) TAL 100 mg; or C) OME 50 mg.kg(-1) for 14 d. Studies of gastric specimens: 1) ulce r size; 2) quantitative histology; 3) expression of EGF mRNAs was determine d by RT/PCR; 4) gastric sections were immunostained with antibodies against EGF and its receptors. In non-ulcerated gastric mucosa of placebo or omepr azole treated group, EGF expression was minimal, while EGF-R was localized to few cells in the mucosal proliferative zone. Gastric ulceration triggere d overexpression of EGF and its receptor in epithelial cells of the ulcer m argin and scar. In ulcerated gastric mucosa TAL treatment significantly enh anced (versus PLA and omeprazole) expression of EGF and EGF-R. OME treatmen t reduced expression of EGF in ulcerated mucosa by 55 +/- 2% (P < 0.01). It is concluded that: 1) treatment with TAL activates genes for EGF and its r eceptor in normal and ulcerated gastric mucosae; 2) since EGF promotes grow th of epithelial cells and their proliferation and migration, the above act ions of TAL provide the mechanism for its ulcer healing action and improved (versus OME) quality of mucosal restoration. (C) 2000 Elsevier Science Ltd . Published by Editions scientifiques et medicales Elsevier SAS.