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

• 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
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2006.08.020

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.