The human trefoil peptide, TFF1, is present in different molecular forms that are intimately associated with mucus in normal stomach

Gut. 2000 Mar;46(3):312-20. doi: 10.1136/gut.46.3.312.

Abstract

Background: TFF1 is a 6.5 kDa secreted protein that is expressed predominantly in normal gastric mucosa. It is coexpressed with mucins and it can form dimers via a free carboxy terminal cysteine residue.

Aims: To investigate the molecular forms of TFF1 that are present in normal human stomach and the association of the different molecular forms with mucus.

Subjects: All subjects had macroscopically normal stomachs at gastroscopy. None had a significant past medical history.

Methods: TFF1 was detected in normal gastric mucosa and adherent mucus by western transfer analysis after electrophoresis on reducing and non-reducing polyacrylamide gels. In some instances, proteins were fractionated by caesium chloride density gradient centrifugation prior to detection of TFF1. The location of TFF1 in gastric mucosa with an intact adherent mucus layer was assessed by immunohistochemistry.

Results: Three different molecular forms of TFF1 were detected: TFF1 monomer, TFF1 dimer, and a TFF1 complex with an apparent molecular mass of about 25 kDa. TFF1 was present at higher concentrations than realised previously. The TFF1 complex was present in the adherent mucus gel layer but while its interaction with mucin was destabilised by caesium chloride, the interaction between mucin and the TFF1 dimer was resistant to caesium chloride.

Conclusions: Most of TFF1 in normal human gastric mucosa is present in a complex that is stabilised by a disulphide bond. TFF1 is intimately associated with mucus. The high concentration, colocalisation, and binding of TFF1 to gastric mucus strongly implicate TFF1 in gastric mucus function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Disulfides / chemistry
  • Electrophoresis, Polyacrylamide Gel
  • Gastric Mucosa / chemistry*
  • Humans
  • Mucus / chemistry
  • Protein Conformation
  • Proteins / analysis
  • Proteins / chemistry*
  • Trefoil Factor-1
  • Tumor Suppressor Proteins

Substances

  • Disulfides
  • Proteins
  • TFF1 protein, human
  • Trefoil Factor-1
  • Tumor Suppressor Proteins