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A gradient of TFF3 (trefoil factor family 3) peptide synthesis within the normal human gastric mucosa

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Abstract

TFF3 is a member of the trefoil factor family (TFF) peptides, which enhance the surface integrity of mucous epithelia, and is typically secreted by intestinal goblet cells together with the mucin MUC2. Reports of the expression of TFF3 within the normal human stomach are contradictory and the precise localisation of TFF3 is unknown. We have mapped the human gastric mucosa by reverse transcription/polymerase chain reaction and Western blot analysis and by immunohistochemistry. Small amounts of TFF3 were detectable in the oxyntic mucosa of the corpus, whereas TFF3 synthesis increased sharply distal to the corpus-antrum transitional zone. TFF3 secretion was demonstrated in the antrum, the pyloric region and the proximal duodenum. High TFF1 levels were present in all regions of the gastric mucosa including the corpus, whereas the proximal duodenum was nearly devoid of TFF1. Immunohistochemistry localised TFF3 to antral and pyloric surface mucous cells. In the antrum, an increasing concentration gradient was found towards cells deeper in the isthmus. TFF1 was confined to superficial pit cells in the antrum. TFF3 was also present in specific layers of the laminated mucous gel of the antral and pyloric regions and variable concentrations of TFF3 (2–62 nmol/l) were measured in gastric juice. Here, a probably N-terminally shortened variant is present that forms disulphide-linked dimers. Thus, TFF3 is a typical secretory peptide of the normal human antral and pyloric gastric mucosa and has a gastric expression pattern different from that of TFF1 and TFF2. TFF3 might therefore have important physiological functions in the stomach, e.g. as a luminal surveillance peptide maintaining particularly the integrity of the antral and pyloric mucosa.

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Acknowledgements

The authors thank B. Glöckner and J. Reising for expert technical assistance, Dr. H. Kalbacher (University Tübingen) for peptide synthesis, Dr. L. Thim (Novo Nordisk) for recombinant human TFF3, and Dr. J. Lindquist for comments on the manuscript.

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Authors and Affiliations

  1. Institut für Molekularbiologie und Medizinische Chemie, Universitätsklinikum, Otto-von-Guericke-Universität, Leipziger Strasse 44, 39120, Magdeburg, Germany

    Irina Kouznetsova & Werner Hoffmann

  2. Klinik für Gastroenterologie, Hepatologie und Infektiologie, Otto-von-Guericke-Universität, 39120, Magdeburg, Germany

    Ulrich Peitz & Peter Malfertheiner

  3. Institut für Pathologie, Otto-von-Guericke-Universität, 39120, Magdeburg, Germany

    Michael Vieth & Albert Roessner

  4. Klinik für Chirurgie, Otto-von-Guericke-Universität, , 39120, Magdeburg, Germany

    Frank Meyer & Hans Lippert

  5. Department of Clinical Biochemistry, Aarhus University Hospital, , 8000, Aarhus, Denmark

    Else Marie Vestergaard

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  1. Irina Kouznetsova
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  2. Ulrich Peitz
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  3. Michael Vieth
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  9. Werner Hoffmann
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Correspondence to Werner Hoffmann.

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This work was supported by grant NBL3/01ZZ0107/PP13 from the Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie (to W. H.) and grants 0163615 and 0500058 from the Fonds der Chemischen Industrie (to W.H.)

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Kouznetsova, I., Peitz, U., Vieth, M. et al. A gradient of TFF3 (trefoil factor family 3) peptide synthesis within the normal human gastric mucosa. Cell Tissue Res 316, 155–165 (2004). https://doi.org/10.1007/s00441-004-0854-1

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