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Interaction of trefoil family factors with mucins: clues to their mechanism of action?
  1. Histopathology Unit, Imperial Cancer Research Fund
  2. London, UK
  3. and Department of Histopathology
  4. Imperial College School of Medicine
  5. Hammersmith Hospital, London, UK

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In recent years there have been numerous reviews and articles describing the distribution of a group of molecules know as thetrefoil peptides ortrefoil family factors (TFFs). In mammals, the family is represented by three members, pS2/TFF1, hSP/TFF2, and ITF/TFF3.1 They are characterised by possession of the TFF motif, a three looped structure held tightly together by disulphide bonds based on six cysteine residues—one such motif in pS2/TFF1 and ITF/TFF3, and two in hSP/TFF2. These molecules are found in the mammalian gastrointestinal tract in more or less defined sites—for example, pS2/TFF1 is located mainly in the foveolar cells of the gastric mucosa, hSP/TFF2 is seen in mucous neck cells, deep pyloric glands, and Brunner's glands, while ITF/TFF3 is expressed predominately in the goblet cells of the small and large intestine. In abnormal situations, as in the ulcer associated cell lineage (UACL) in Crohn's disease, or in the epithelium seen migrating over the surface of healing peptic ulcers, all three TFFs can be expressed.2 Indeed, there is evidence for coordinated expression of TFFs, at least in transfected cell lines.3

Experiments in polarised epithelial monolayers in vitro show that TFFs promote cell migration and are therefore thought to promote epithelial restitution after damage.4 ,5 Mice over expressing pS2/TFF1 in the small intestine are more resistant to induced damage6 whereas mice in which ITF/TFF3 has been knocked out by gene targeting show reduced resistance.7 When the pS2/TFF1 gene was deleted, mice showed pronounced gastric and small intestinal mucosal inflammation, with the development of adenomas and occasional intramucosal carcinomas in the antrum.8

But there is no general agreement about the mode of action of trefoil factors on epithelial …

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