ChemInform Abstract: Trefoil Factor Family (TFF) Peptides and Chemokine Receptors: A Promising Relationship.

ChemInform ◽  
2010 ◽  
Vol 41 (9) ◽  
Author(s):  
Werner Hoffmann
Keyword(s):  
Chemokine Receptors ◽  
Trefoil Factor ◽  
Trefoil Factor Family ◽  
Tff Peptides

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

2020 ◽  
Vol 21 (12) ◽  
pp. 4535 ◽  
Author(s):  
Werner Hoffmann
Keyword(s):  
Thiol Group ◽  
Suppressor Gene ◽  
Immune Defense ◽  
Trefoil Factor ◽  
Gastric Mucus ◽  
Free Thiol Group ◽  
Trefoil Factor Family ◽  
Molecular Functions ◽  
Mucus Barrier ◽  
Tff Peptides

Trefoil factor family peptides (TFF1, TFF2, TFF3) are typically co-secreted together with mucins. Tff1 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 Helicobacter pylori (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.

Trefoil factor family peptides – friends or foes?

2015 ◽  
Vol 6 (5-6) ◽  
pp. 343-359 ◽  
Author(s):  
Maike Busch ◽  
Nicole Dünker
Keyword(s):  
Cancer Research ◽  
Tumor Suppressors ◽  
Current Knowledge ◽  
Tumor Biology ◽  
Epigenetic Mechanisms ◽  
Trefoil Factor ◽  
Protective Function ◽  
Trefoil Factor Family ◽  
Tff Peptides

AbstractTrefoil factor family (TFF) peptides are a group of molecules bearing a characteristic three-loop trefoil domain. They are mainly secreted in mucous epithelia together with mucins but are also synthesized in the nervous system. For many years, TFF peptides were only known for their wound healing and protective function, e.g. in epithelial protection and restitution. However, experimental evidence has emerged supporting a pivotal role of TFF peptides in oncogenic transformation, tumorigenesis and metastasis. Deregulated expression of TFF peptides at the gene and protein level is obviously implicated in numerous cancers, and opposing functions as oncogenes and tumor suppressors have been described. With regard to the regulation of TFF expression, epigenetic mechanisms as well as the involvement of various miRNAs are new, promising aspects in the field of cancer research. This review will summarize current knowledge about the expression and regulation of TFF peptides and the involvement of TFF peptides in tumor biology and cancerogenesis.

Synthesis and localization of trefoil factor family (TFF) peptides in the human urinary tract and TFF2 excretion into the urine

2010 ◽  
Vol 339 (3) ◽  
pp. 639-647 ◽  
Author(s):  
Margarita Rinnert ◽  
Margitta Hinz ◽  
Peter Buhtz ◽  
Frank Reiher ◽  
Wolfgang Lessel ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Trefoil Factor ◽  
Trefoil Factor Family ◽  
Tff Peptides

Trefoil factor family (TFF) peptides and cancer progression

Peptides ◽  
2004 ◽  
Vol 25 (5) ◽  
pp. 885-898 ◽  
Author(s):  
Shahin Emami ◽  
Sylvie Rodrigues ◽  
Christelle M Rodrigue ◽  
Nathalie Le Floch ◽  
Christine Rivat ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Trefoil Factor ◽  
Trefoil Factor Family ◽  
Tff Peptides

scholarly journals Human Synovia Contains Trefoil Factor Family (TFF) Peptides 1–3 Although Synovial Membrane Only Produces TFF3: Implications in Osteoarthritis and Rheumatoid Arthritis

2019 ◽  
Vol 20 (23) ◽  
pp. 6105
Author(s):  
Popp ◽  
Schicht ◽  
Garreis ◽  
Klinger ◽  
Gelse ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Real Time ◽  
Real Time Pcr ◽  
Synovial Membrane ◽  
Mrna Level ◽  
Trefoil Factor ◽  
Healthy Donors ◽  
Trefoil Factor Family ◽  
Secretion Product ◽  
Tff Peptides

Objective: Trefoil factor family peptide 3 (TFF3) has been shown to support catabolic functions in cases of osteoarthritis (OA). As in joint physiology and diseases such as OA, the synovial membrane (SM) of the joint capsule also plays a central role. We analyze the ability of SM to produce TFF compare healthy SM and its secretion product synovial fluid (SF) with SM and SF from patients suffering from OA or rheumatoid arthritis (RA). Methods: Real-time PCR and ELISA were used to measure the expression of TFFs in healthy SM and SM from patients suffering from OA or RA. For tissue localization, we investigated TFF1-3 in differently aged human SM of healthy donors by means of immunohistochemistry, real-time PCR and Western blot. Results: Only TFF3 but not TFF1 and -2 was expressed in SM from healthy donors as well as cases of OA or RA on protein and mRNA level. In contrast, all three TFFs were detected in all samples of SF on the protein level. No significant changes were observed for TFF1 at all. TFF2 was significantly upregulated in RA samples in comparison to OA samples. TFF3 protein was significantly downregulated in OA samples in comparison to healthy samples and cases of RA significantly upregulated compared to OA. In contrast, in SM TFF3 protein was not significantly regulated. Conclusion: The data demonstrate the production of TFF3 in SM. Unexpectedly, SF contains all three known TFF peptides. As neither articular cartilage nor SM produce TFF1 and TFF2, we speculate that these originate with high probability from blood serum.

scholarly journals Trefoil Factor Family (TFF) Peptides

Encyclopedia ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 974-987
Author(s):  
Werner Hoffmann
Keyword(s):  
Immune Defense ◽  
Innate Immune ◽  
Amino Acid Residues ◽  
Trefoil Factor ◽  
Gastric Mucus ◽  
Lectin Activity ◽  
Exocrine Products ◽  
Trefoil Factor Family ◽  
Tff Domain ◽  
Tff Peptides

Trefoil factor family (TFF) peptides mainly consist of characteristic TFF domains, which contain about 40 amino acid residues, including 6 conserved cysteine residues. TFF peptides possess a single (mammalian TFF1 and TFF3), two (mammalian TFF2, Xenopus laevis xP2) or four TFF domains (X. laevis xP4). They exhibit lectin activities and are characteristic exocrine products of the mucous epithelia. Here, they play different roles for mucosal protection and the innate immune defense: TFF1 is a gastric tumor suppressor; TFF2 builds a lectin complex with the mucin MUC6, physically stabilizing the inner gastric mucus layer; and TFF3 forms a disulfide-linked heterodimer with IgG Fc binding protein (FCGBP), probably preventing the infiltration of microorganisms. Minor amounts of TFF peptides are endocrine products of the immune and nervous systems. Pathologically, TFF peptides are linked to inflammation. There are increasing indications that TFF peptides can antagonize cytokine receptors, such as receptors for IL-1β, IL-6, and TNFα (thereby acting as anti-inflammatory peptides). TFF peptides can probably also activate a variety of receptors, such as CXCR4. The TFF domain is a unique shuffled module which is also present in a number of mosaic proteins, such as zona pellucida proteins, sugar degrading enzymes and frog skin mucins. Here, their function seems to be defined by a lectin activity, which might even allow a role in fertilization.

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