Effect of trefoil factors on the viscoelastic properties of mucus gels.
BACKGROUND
Trefoil peptides (TFFs) are expressed and secreted in a tissue-specific manner in the gastrointestinal tract. Evidence of coexpression of trefoil peptides and mucins has been demonstrated in most mucus-producing cells in the gastrointestinal tract. The expression of trefoil peptides is up-regulated in gastric ulceration and colitis. It is believed that TFF peptides interact with mucin to increase viscosity but this has never been confirmed. The aims of the present study were to elucidate the direct effect of trefoil peptides on mucus gel formation.


METHODS
The viscosity of mucin solutions was measured by means of a rotational rheometer after adding three mammalian trefoil peptides: TFF1, TFF2, and TFF3.


RESULTS
Adding TFF2 (0.3%) to the mucin solutions (8%) resulted in more than a factor 10 increase in viscosity and elasticity, and the mucin solution was transformed into a gel-like structure with serpentine-like complexes between the mucin and TFF2. The dimer form of TFF3 also increased viscosity but resulted in a spider's web-like structure. The monomer forms of TFF1 and TFF3 had very little effect on the viscosity and elasticity of the mucin solutions.


CONCLUSIONS
The addition of TFF2 to mucin solutions results in significantly increased viscosity and elasticity, under which the mucin solutions are transformed into a gel-like state. The ability of some trefoil peptides to catalyse the formation of stable mucin complexes may be one of the ways by which these peptides exert their protective and healing functions.
Thim
L
L
Novo Nordisk A/S, Bagsvaerd, Denmark. LTH@novonordisk.com
Madsen
F
F
Poulsen
S S
SS
D000818:Animals; D002417:Cattle; D004548:Elasticity / Q000187:drug effects; D005782:Gels; D006133:Growth Substances / Q000032:analysis / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D009077:Mucins / Q000502:physiology*; D009124:Muscle Proteins; D009479:Neuropeptides; D010455:Peptides / Q000032:analysis / Q000494:pharmacology*; D011506:Proteins; D012212:Rheology; D013183:Sputum; D013552:Swine; D000071163:Trefoil Factor-1; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D025521:Tumor Suppressor Proteins; D014783:Viscosity / Q000187:drug effects
D005782:Gels; D006133:Growth Substances; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010455:Peptides; D011506:Proteins; C051838:TFF1 protein, human; C000604007:TFF2 protein, human; C099037:TFF3 protein, rat; C000604008:Tff2 protein, rat; D000071163:Trefoil Factor-1; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D025521:Tumor Suppressor Proteins