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

Citation

Marchbank, T and Cox, HM and Goodlad, RA and Giraud, AS and Moss, SF and Poulsom, R and Wright, NA and Jankowski, J and Playford, RJ, Effect of ectopic expression of rat trefoil factor family 3 (intestinal trefoil factor) in the jejunum of transgenic mice, Journal of Biological Chemistry, 276, (26) pp. 24088-24096. ISSN 0021-9258 (2001) [Refereed Article]

DOI: doi:10.1074/jbc.M101363200

Abstract

To further examine the function of the trefoil factor family (TFF), the expression of which is up-regulated at sites of injury, we have produced transgenic mice that chronically express rat TFF3 within the jejunum (using a rat fatty acid-binding protein promoter). The expression of rat TFF3 was limited 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 indomethacin (85 mg/kg subcutaneously), which only caused a 29% reduction in villus height in transgenics versus 51% reduction in controls (p < 0.01). Indomethacin increased initial intestinal epithelial cell proliferation and migration, but the presence of rat TFF3 caused no additional change in proliferation (bromodeoxyuridine), cell migration ([3H]thymidine and bromodeoxyuridine), apoptosis (terminal deoxyuridine nucleotidyl nick end labeling), or E-cadherin immunostaining. In vitro studies following changes in resistance of intestinal strips in Ussing chambers (voltage-clamp technique) showed increased base-line resistance in the rat TFF3-expressing region (326 ± 60 versus 195 ± 48 ohm·cm2 in controls, p < 0.05) and reduced the fall in resistance following HCl 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.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Medical Biochemistry and Metabolomics
Research Field:Medical Biochemistry: Proteins and Peptides (incl. Medical Proteomics)
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Digestive System Disorders
Author:Playford, RJ (Professor Ray Playford)
ID Code:72891
Year Published:2001
Web of Science® Times Cited:41
Deposited By:Research Division
Deposited On:2011-09-02
Last Modified:2011-09-05
Downloads:0

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