Trefoil Factor Family (TFF) Peptides and Their Diverse Molecular Functions in Mucus Barrier Protection and More: Changing the Paradigm

• Published in: International journal of molecular sciences 2020-06, Vol.21 (12), p.4535
• Main Author: Hoffmann, Werner
• Format: Article
• Language: English
• Subjects: Amino acids; Animals; Apoptosis; Carbohydrates; Carrier Proteins - metabolism; Cell adhesion & migration; Cytokines; Disease; Epidermal growth factor; Esophagus; Fc receptors; Gastric cancer; Gastric mucosa; Gastric Mucosa - metabolism; Genotype & phenotype; Helicobacter pylori - metabolism; Humans; Immune system; Immunoglobulin G; Infections; inflammation; Inflammatory bowel disease; lectin; Lipopolysaccharides; Metastases; Microorganisms; Morphology; Mucin; Mucins - metabolism; Mucous Membrane - metabolism; Mucous Membrane - physiology; Mucus; Mucus - metabolism; Mutation; Peptides; Proteins; reactive nitrogen species; reactive oxygen species; Review; Stomach - pathology; Trefoil factor; Trefoil Factor-1 - metabolism; Trefoil Factor-2 - metabolism; Trefoil Factor-3 - metabolism; Trefoil Factors - genetics; Trefoil Factors - metabolism; Trefoil Factors - physiology; Tumor suppressor genes; Tumor Suppressor Proteins - metabolism; Tumorigenesis; Tumors; Wound healing
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21124535

Trefoil factor family peptides (TFF1, TFF2, TFF3) are typically co-secreted together with mucins. represents a gastric tumor suppressor gene in mice. TFFs are also synthesized in minute amounts in the immune and central nervous systems. In mucous epithelia, they support rapid repair by enhancing cell migration ("restitution") via their weak chemotactic and anti-apoptotic effects. For a long time, as a paradigm, this was considered as their major biological function. Within recent years, the formation of disulfide-linked heterodimers was documented for TFF1 and TFF3, e.g., with gastrokine-2 and IgG Fc binding protein (FCGBP). Furthermore, lectin activities were recognized as enabling binding to a lipopolysaccharide of (TFF1, TFF3) or to a carbohydrate moiety of the mucin MUC6 (TFF2). Only recently, gastric TFF1 was demonstrated to occur predominantly in monomeric forms with an unusual free thiol group. Thus, a new picture emerged, pointing to diverse molecular functions for TFFs. Monomeric TFF1 might protect the gastric mucosa as a scavenger for extracellular reactive oxygen/nitrogen species. Whereas, the TFF2/MUC6 complex stabilizes the inner layer of the gastric mucus. In contrast, the TFF3-FCGBP heterodimer (and also TFF1-FCGBP) are likely part of the innate immune defense of mucous epithelia, preventing the infiltration of microorganisms.