Effect of ectopic expression of rat trefoil factor family 3 (intestinal trefoil factor) in the jejunum of transgenic mice

To further examine the function of the trefoil factor family (TFF), the exp ression of which is up-regulated at sites of injury, we have produced trans genic mice that chronically express rat TFF3 within the jejunum (using a ra t fatty acid-binding protein promoter). The expression of rat TFF3 was limi ted to the villi of the jejunum and had no effect on base-line morphology. Rat TFF3 expression did result, however, in a reduced sensitivity to indome thacin (85 mg/kg sulbcutaneously), which only caused a 29% reduction in vil lus height in transgenics versus 51% reduction in controls (p < 0.01). Indo methacin increased initial intestinal epithelial cell proliferation and mig ration, but the presence of rat TFF3 caused no additional change in prolife ration (bromodeoxyuridine), cell migration ([H-3]thymidine and bromodeoxyur idine), apoptosis (terminal deoxyuridine nucleotidyl nick end labeling), or E-cadherin immunostaining, In vitro studies following changes in resistanc e of intestinal strips in Ussing chambers (voltage-clamp technique) showed increased base-line resistance in the rat TFF3-expressing region (326 +/- 6 0 versus 195 +/- 48 ohm.cm(2) in controls, p < 0.05) and reduced the fall i n resistance following Hel exposure by about 40% (p < 0.01). Overexpression of TFF3 stabilizes the mucosa against noxious agents, supporting its role in mucosal protection/repair. It may therefore provide a novel approach to the prevention and/or treatment of intestinal ulceration.