Rebamipide treatment activates epidermal growth factor and its receptor expression in normal and ulcerated gastric mucosa in rats: one mechanism for its ulcer healing action?

Rebamipide (Mucosta) is a novel mucosal protective and ulcer-healing drug. Clinical and experimental data indicate that it accelerates ulcer healing and improves the quality of the scar. Since epidermal growth factor (EGF) and its receptor (EGF-R) play important roles in mucosal protection and ulcer healing, we studied whether rebamipide treatment affects expression of EGF and EGF-R in normal and ulcerated gastric mucosa in rats. Forty-eight male rats without or with gastric ulcers (induced by acetic acid) received intragastrically either placebo or rebamipide, 40 mg twice daily, for 14 days. Ulcer size was measured under a dissecting microscope; mucosal sections were stained with H&E or immunostained with specific antibodies against EGF and EGF-R. The distribution and intensity of fluorescence signal was quantified using a video image system. Rebamipide significantly accelerated ulcer healing, produced a significant increase in EGF and EGF-R expression in normal gastric mucosa (both P < 0.001), and increased expression of EGF and EGF-R in regenerating glands of the ulcer scar. Since EGF and its receptor are crucial for epithelial cell proliferation, re-epithelialization, and gland reconstruction, the above actions of rebamipide may provide a new mechanism for its ulcer healing action.