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Science 11 October 1996:
Vol. 274. no. 5285, pp. 262 - 265
DOI: 10.1126/science.274.5285.262
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Reports

Impaired Defense of Intestinal Mucosa in Mice Lacking Intestinal Trefoil Factor

Hiroshi Mashimo, Deng-Chyang Wu, Daniel K. Podolsky, * Mark C. Fishman

The mechanisms that maintain the epithelial integrity of the gastrointestinal tract remain largely undefined. The gene encoding intestinal trefoil factor (ITF), a protein secreted throughout the small intestine and colon, was rendered nonfunctional in mice by targeted disruption. Mice lacking ITF had impaired mucosal healing and died from extensive colitis after oral administration of dextran sulfate sodium, an agent that causes mild epithelial injury in wild-type mice. ITF-deficient mice manifested poor epithelial regeneration after injury. These findings reveal a central role for ITF in the maintenance and repair of the intestinal mucosa.

H. Mashimo, D.-C. Wu, D. K. Podolsky, Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Jackson 7, Massachusetts General Hospital, Fruit Street, Boston, MA 02114, USA.
M. C. Fishman, Cardiovascular Research Center, Massachusetts General Hospital East, 149 13th Street, Charlestown, MA 02129, USA.
*   To whom correspondence should be addressed.

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Distribution and metabolism of intravenously administered trefoil factor 2/porcine spasmolytic polypeptide in the rat.
S S Poulsen, J Thulesen, E Nexo, and L Thim (1998)
Gut 43, 240-247
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Modulation of Epithelial Cell Adhesion in Gastrointestinal Homeostasis.
J. A. Efstathiou and M. Pignatelli (1998)
Am. J. Pathol. 153, 341-347
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Short-chain fatty acids inhibit intestinal trefoil factor gene expression in colon cancer cells.
C. P. Tran, M. Familari, L. M. Parker, R. H. Whitehead, and A. S. Giraud (1998)
Am J Physiol Gastrointest Liver Physiol 275, G85-G94
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Intestinal trefoil factor controls the expression of the adenomatous polyposis coli-catenin and the E-cadherin-catenin complexes in human colon carcinoma cells.
J. A. Efstathiou, M. Noda, A. Rowan, C. Dixon, R. Chinery, A. Jawhari, T. Hattori, N. A. Wright, W. F. Bodmer, and M. Pignatelli (1998)
PNAS 95, 3122-3127
   Abstract »    Full Text »    PDF »
Identification of a Goblet Cell-specific Enhancer Element in the Rat Intestinal Trefoil Factor Gene Promoter Bound by a Goblet Cell Nuclear Protein.
H. Ogata, N. Inoue, and D. K. Podolsky (1998)
J. Biol. Chem. 273, 3060-3067
   Abstract »    Full Text »    PDF »
Intestinal trefoil factor induces inactivation of extracellular signal-regulated protein kinase in intestinal epithelial cells.
M. Kanai, C. Mullen, and D. K. Podolsky (1998)
PNAS 95, 178-182
   Abstract »    Full Text »    PDF »
Toward Better Treatment of Primary Sclerosing Cholangitis.
M. M. Kaplan (1997)
N. Engl. J. Med. 336, 719-721
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Trefoil Peptides in the Defense of the Gastrointestinal Tract.
A. G. Plaut (1997)
N. Engl. J. Med. 336, 506-507
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Effect of Ectopic Expression of Rat Trefoil Factor Family 3 (Intestinal Trefoil Factor) in the Jejunum of Transgenic Mice.
T. Marchbank, H. M. Cox, R. A. Goodlad, A. S. Giraud, S. F. Moss, R. Poulsom, N. A. Wright, J. Jankowski, and R. J. Playford (2001)
J. Biol. Chem. 276, 24088-24096
   Abstract »    Full Text »    PDF »


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