Abstract
TFF1 is a protective peptide of the Trefoil Factor Family (TFF), which is co-secreted with the mucin MUC5AC, gastrokine 2 (GKN2), and IgG Fc binding protein (FCGBP) from gastric surface mucous cells. Tff1-deficient mice obligatorily develop antropyloric adenoma and about 30% progress to carcinomas, indicating that Tff1 is a tumor suppressor. As a hallmark, TFF1 contains seven cysteine residues with three disulfide bonds stabilizing the conserved TFF domain. Here, we systematically investigated the molecular forms of TFF1 in the human gastric mucosa. TFF1 mainly occurs in an unusual monomeric form, but also as a homodimer. Furthermore, minor amounts of TFF1 form heterodimers with GKN2, FCGBP, and an unknown partner protein, respectively. TFF1 also binds to the mucin MUC6 in vitro, as shown by overlay assays with synthetic 125I-labeled TFF1 homodimer. The dominant presence of a monomeric form with a free thiol group at Cys-58 is in agreement with previous studies in Xenopus laevis and mouse. Cys-58 is likely highly reactive due to flanking acid residues (PPEEEC58EF) and might act as a scavenger for extracellular reactive oxygen/nitrogen species protecting the gastric mucosa from damage by oxidative stress, e.g., H2O2 generated by dual oxidase (DUOX).
Highlights
The secretory peptide TFF1 is a member of the Trefoil Factor Family (TFF) [1,2,3]
TFF1 is a protective peptide of the Trefoil Factor Family (TFF), which is co-secreted with the mucin MUC5AC, gastrokine 2 (GKN2), and IgG Fc binding protein (FCGBP) from gastric surface mucous cells
It would be promising to study whether synthetic peptides mimicking the C-terminal region of TFF1 are able to reduce oral mucositis
Summary
The secretory peptide TFF1 (formerly: pS2) is a member of the Trefoil Factor Family (TFF) [1,2,3]. The biological function of TFF1 was mainly attributed to its rather weak motogenic effect in vitro (chemotactic factor) [1,2,3,10,18,19,20,21,22,23] This activity together with an anti-apoptotic effect [24] would be capable of enhancing the rapid repair of the gastric mucosa after damages by cell migration, a process called “restitution” [25,26]. Here, we systematically investigated the different forms of TFF1 in human gastric mucosa using anion-exchange and size exclusion chromatography (SEC), and performed binding studies with synthetic TFF1. This is a further step towards understanding the molecular function of TFF1, as a gastric tumor suppressor
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