Expression of intestinal trefoil factor in early repairing process of acute gastric mucosal damage induced, by indomethacin in rat

Abstract

Backeround & Aims; Trefoil peptides such as pS2, PSP, and intestinal trefoil factor (ITF) are a relatively new group of peptides which have been shown to prevent and/or ameliorate gastric mucosal injury induced by ethanol and by NSAIDs. They may also serve to reseal mucosal wounds, influence cell proliferation, and accelerate the migration of proliferating epithelial cells in humans and mice. All are considered to be tissue-specific, and ITF is shown to be produced by goblet ceils in the normal intestinal mucosa and to be delivered with mucin glycoprotein. However, it has not been fully examined whether ITF is expressed constitutively in the stomach. Moreover, a possible role of ITF expression in repairing process of gastric mucosal injury remains undetermined. In the present study, a model of acute gastric mucosal damage in the rat was used to examine the expression of ITF which may play an active part in the healing response. Methods: Acute g~/stric mucosal damage was induced by intragastric administration of indomethacin (20 mg/kg). The expression of ITF was monitored over the next 72 hours using immunohistochernistry, and was assessed quantitatively by measuring proportion of ITF-positive area (%) to the background on the samples with immunohistochemical staining. The expression of proliferating cell nuclear antigen (PCNA) was also examined. Re$ult$: (1) In the normal gastroduodenal rnucosa, ITF immunoreactivity was present strongly at the glandular bases of the gastric body, weakly at the glandular necks, and most strongly within the duodenal glands (linked with mucin glycoprntein). No immunostaining was seen in the bulk of the gastric surface epithelium. (2) Administration of indomethacin induced hemorrhagic lesions over the body after 3 hrs, erosions and ulcerations over the antrum after 24 hrs, and reepithelialization of the ulcerations after 72 hrs. (3) Three hours after ulcer induction, enhanced immunoreactivity of ITF was not detected. Twenty four hours or later after induction, immunoreactive ITF was enhanced not only in the mucous neck cells, but also at the glandular bases. ITF-positive area at the ulcer beds was 0% after 3 and 24 hrs, and 0.8% after 72 hrs. In contrast, ITF-positive area at the ulcer edges increased in a time-related fashion (0%, 3.3% and 8.4% after 3, 24 and 72 hrs, respectively), whereas it did not change at non-ulcerated regions during the period. (4) PCNA labeling index at the ulcer edge increased, corresponding with enhanced immunoreactivity of ITF. Conclusions: The localization of ITF to the normal gastric epithelium, particularly the bases of fundic glands, raises the possibility that ITF may act as a regulator of secretory function. The pronounced expression of ITF around the ulcerations after induction of gastric injury suggests that ITF peptide may play a significant role in the repair-accelerating mechanisms, and also in the later ulcer-healing processes in the stomach.