TFF3-peptide increases transepithelial resistance in epithelial cells by modulating claudin-1 and -2 expression

TFF3 plays an important role in the protection and repair of the gastrointestinal mucosa. The molecular mechanisms of TFF function, however, are still largely unknown. Increasing evidence indicates that apart from stabilizing mucosal mucins TFF3 induces cellular signals that modulate cell–cell junct...

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Bibliographic Details
Published in:Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2006-12, Vol.27 (12), p.3383-3390
Main Authors: Meyer zum Büschenfelde, Dirk, Tauber, Rudolf, Huber, Otmar
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cell Line
Cell Membrane Permeability - physiology
Claudin
Claudin-1
Claudins
Dogs
Epithelial barrier
Epithelial Cells - metabolism
Fundamental and applied biological sciences. Psychology
HT29 Cells
Humans
Intestinal Mucosa - cytology
Intestinal Mucosa - metabolism
Membrane Proteins - genetics
Membrane Proteins - metabolism
Occludin
Peptides - genetics
Peptides - physiology
TFF3
Tight junction
Tight Junctions - metabolism
Trefoil Factor-3
Vertebrates: endocrinology
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Summary:TFF3 plays an important role in the protection and repair of the gastrointestinal mucosa. The molecular mechanisms of TFF function, however, are still largely unknown. Increasing evidence indicates that apart from stabilizing mucosal mucins TFF3 induces cellular signals that modulate cell–cell junctions of epithelia. In transfected HT29/B6 and MDCK cells stably expressing FLAG-tagged human TFF3 we have recently shown that TFF3 down-regulates E-cadherin, impairs the function of adherens junctions and thus facilitates cell migration in wounded epithelial cell layers. Here we investigate TFF3-induced effects on the composition and function of tight junctions in these cells. TFF3 increased the cellular level of tightening claudin-1 and decreased the amount of claudin-2 known to form cation-selective channels. Expression of ZO-1, ZO-2 and occludin was not altered. The change in claudin-1 and -2 expression in TFF3-expressing HT29/B6 cells was accompanied by an increase in the transepithelial resistance in confluent monolayers of these cells. These data suggest that TFF3 plays a role in the regulation of intestinal barrier function by altering the claudin composition within tight junctions thus decreasing paracellular permeability of the intestinal mucosa.
ISSN:0196-9781
1873-5169
DOI:10.1016/j.peptides.2006.08.020