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Tissue Localization of Human Trefoil Factors 1, 2, and 3

Jens Madsen, Ole Nielsen, Ida Tornøe, Lars Thim and Uffe Holmskov

Cardiovascular Research Institute, University of California San Francisco, San Francisco, California (JM); Department of Pathology, Odense Universitetshospital, Odense, Denmark (ON); Medical Biotechnology Center, University of Southern Denmark, Odense, Denmark (IT,UH); and Department of Protein Engineering, Novo Nordisk A/S, Måløv, Denmark (LT)

Correspondence to: Jens Madsen, Cardiovascular Research Institute, University of California San Francisco, 333 California St., San Francisco, CA 94118. E-mail: jens.madsen{at}ucsf.edu

Trefoil factors (TTFs) are small, compact proteins coexpressed with mucins in the gastrointestinal tract. Three trefoil factors are known in mammals: TFF1, TFF2, and TFF3. They are implicated to play diverse roles in maintenance and repair of the gastrointestinal channel. We compared the expression pattern of the three trefoil factors analyzing mRNA from a panel of 20 human tissues by conventional reverse transcriptase (RT) PCR and, in addition, by real-time PCR. These findings were supported by immunohistochemical analysis of paraffin-embedded human tissues using rabbit polyclonal antibodies raised against these factors. TFF1 showed highest expression in the stomach and colon, whereas TFF2 and TFF3 showed highest expression in stomach and colon, respectively. All three TFFs were found in the ducts of pancreas. Whereas TFF2 was found to be restricted to these two tissues, the structurally more closely related TFF1 and TFF3 showed a more general tissue distribution and were found to colocalize on an array of mucosal surfaces. This is the first thorough parallel description of the tissue distribution of TFFs in normal tissues, and it provides a baseline for similar analysis in diseased tissues. (J Histochem Cytochem 55:505–513, 2007)

Key Words: trefoil factor • mucosal • innate immunity • tissue localization • real-time PCR • immunohistochemistry

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