Dimerization of human pS2 (TFF1) plays a key role in its protective/healing effects

230

252

The trefoil factor family (TFF) comprises a group of small peptides which are highly expressed in tissues containing mucus-producing cells - especially in the mucosa lining the gastrointestinal tract. The peptides seem crucial for epithelial restitution and may work via other pathways than the conventional factors involved in restitution. In vitro studies have shown that the TFFs promote restitution using multiple mechanisms. The peptides also have other functionalities including interactions with the immune system. Moreover, therapeutic effects of the TFFs have been shown in several animal models of gastrointestinal damage. Still it is not clear which of their in vitro properties are involved in the in vivo mode of action. This review describes the TFF family with emphasis on their biological properties and involvement in mucosal protection and repair.

Section: Effect Of Tffs In Animal Models Of Diseasementioning

confidence: 92%

“…Oral TFF2 in the same low doses as given systemically had no effect. Using the same model, subcutaneous TFF1 and TFF3 were also effective, the hTFF1 dimer being more potent than the monomer [163,164] . There was a synergistic effect of the combination of TFF3 and EGF, thus supporting in vitro data [163] .…”

Section: Effect Of Tffs In Animal Models Of Diseasementioning

confidence: 96%

The trefoil factor family – small peptides with multiple functionalities

Kjellev¹

2008

230

252

“…Studies with recombinant TFF1 have shown that the C-terminal cysteine forms intermolecular disulphide bonds to produce TFF1 homo-dimers [20]. The TFF1 dimer has greater activity that the TFF1 monomer both in vitro and in an animal model [19,21]. In normal human gastric mucosa, TFF1 is present in three molecular forms: as TFF1 monomer, TFF1 homo-dimer and as an ~25-kDa complex that is stabilised by a disulphide bond, with another as yet unidentified protein [22].…”

mentioning

confidence: 99%

The trefoil protein TFF1 is bound to MUC5AC in humangastric mucosa

Ruchaud-Sparagano

Westley

May

2004

The trefoil protein TFF1 is expressed principally in the superficial cells of the gastric mucosa. It is a small protein and forms homo- and hetero-dimers via a disulphide bond through Cys58 which is located three amino acids from the C terminus. TFF1 is co-expressed with the secreted mucin MUC5AC in superficial cells of the gastric mucosa suggesting that it could be involved in the packaging or function of gastric mucus. We have previously shown that TFF1 co-sediments with mucin glycoproteins on caesium chloride gradients. To extend this observation we have now used gel filtration under physiological conditions, immunoprecipitation and Western transfer analysis to characterise the interaction of TFF1 with gastric mucin glycoproteins. We show that TFF1 co-elutes with MUC5AC but not MUC6 on gel filtration and that immunoprecipitation and Western transfer analysis confirms that TFF1 interacts with MUC5AC. We also demonstrate that the TFF1 dimer is the predominant molecular form bound to MUC5AC. Salt and chelators of divalent cations such as EDTA and EGTA disrupted the TFF1- MUC5AC interaction and increased the degradation of MUC5AC, whereas calcium increased the amount of TFF1 bound to MUC5AC. These data support the contention that TFF1 is pivotal in the packaging and function of human gastric mucosa.

“…In a wounding model of restitution with the human colorectal cell line HT29, the extent of migration was increased in the presence of TFF1 dimer but not monomer [47]. Both forms of TFF1 inhibited the growth of the human gastric cell line AGS, but the dimer was more potent and effected a greater inhibition in cell growth [48].…”

Section: Activities In Vitromentioning

confidence: 97%

Trefoil factors

Thim

May²

2005

130

The present review will include the mammalian trefoil factors, TFF1, TFF2 and TFF3. It will summarise the amino acid sequences from different species, their posttranslational modifications and their structures determined by X-ray analysis and nuclear magnetic resonance studies. Trefoil factors all have a well-defined, structurally conserved trefoil domain. The trefoil domain consists of 42 or 43 amino acid residues and contains 6 cysteine residues that form disulphide bonds in a 1-5, 2-4 and 3-6 configuration. By the establishment of an additional intra-molecular disulphide bond at the C-terminal end, TFF1 and TFF3 form homodimers or heterodimers. This dimer formation of TFF1 and TFF3 will be discussed, and the possible implications for biological activity will be reviewed. The physicochemical characteristics including protease stability of trefoil factors will be summarised. The biological implications of different molecular forms of trefoil factors and their interaction with mucins will be discussed together with other functional insights.