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.
Tarnawski
A
A
VA Medical Center, Long Beach, California 90822, USA.
Arakawa
T
T
Kobayashi
K
K
D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004815:Epidermal Growth Factor / Q000096:biosynthesis / Q000378:metabolism*; D066246:ErbB Receptors / Q000096:biosynthesis / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D008297:Male; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000378:metabolism
D000897:Anti-Ulcer Agents; D015363:Quinolones; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; C052785:rebamipide; D000409:Alanine