Human Trefoil Factor 2 Is a Lectin That Binds α-GlcNAc-capped Mucin Glycans with Antibiotic Activity against Helicobacter pylori

Abstract

Background: Trefoil factor 2 (TFF2) forms complexes with MUC6 and is concertedly secreted by deep gastric glands. Results: TFF2 is a lectin that binds to ␣-GlcNAc-capped MUC6 O-glycans with antibiotic activity against Helicobacter pylori. Conclusion: There may be a functional link between mucin glycans and TFF2 in H. pylori defense. Significance: The findings impact in development of defense strategies against H. pylori and in TFF2 receptor-mediated cell signaling.

Trefoil factors: Gastrointestinal-specific proteins associated with gastric cancer

“…This would mean that undefined membrane-bound mucins or non-mucin-type glycoproteins expressing the TFF2 binding glycotope may act as candidates of trefoil factor receptors [107]. Additionally, TFF3 coexpresses with the intestinal-type mucin, MUC2, and they are both elevated in GCs [108] (Fig.…”

Trefoil Factor Peptides and Gastrointestinal Function

“…In all cases the TFF is stored and secreted from the same cells as the mucin protein. TFF1 colocalizes with MUC5AC in the gastric surface epithelium, TFF2 with MUC6 in the gastric pit to deep gland and neck cells, and TFF3 with MUC2 in the intestine (3, 62–64). In some cases it is clear that the TFF is cosecreted with the mucin, such as TFF3 being cosecreted with MUC2 from the goblet cell (10).…”

“…H. pylori infected stomach in Tff1 KO mice showed an enhanced inflammation and invasive gastric adenocarcinoma (128). TFF2 specifically binds to O -linked α1,4-GlcNAc-capped MUC6 glycan, which is speculated to have a potential antibiotic activity against H. pylori (64). H. pylori infection for 12 and 15 months in normal mouse stomach reduced antral expression of Tff2 by increased methylation at Tff2 promoter site, mirroring the findings in human samples (130).…”

TFF2, a MUC6-binding lectin stabilizing the gastric mucus barrier and more (Review)

“…With the help of TFF2 fusion proteins, the carbohydrate specificity was narrowed down in a porcine gastric mucin preparation to GlcNAcα1→4Galβ1→4GlcNAcβ with only minor crossreactivity to GlcNAcα1→4Galβ, which points to an extended glycotope that comprises more than a common disaccharide (88). The GlcNAcα1→4Galβ1→4GlcNAcβ glycotope has been described previously as part of core 2 mucin structures from human and porcine stomach (56,89) as well as from duodenal Brunner's glands, which also secrete MUC6 (90).…”