TFF3 and EGF Induce Different Migration Patterns of Intestinal Epithelial Cells <i>In Vitro</i> and Trigger Increased Internalization of E-cadherin

Abstract

Background/Aims: TFF3, a member of the TFF (trefoil factor family) peptides, and epidermal growth factor (EGF) actively support the repair of mucosal barriers, particularly during restitution. The aim of this study was to compare the motogenic effects of TFF3 and EGF. Methods: The influence of recombinant human TFF3 (dimeric form) and EGF on the migration of IEC-18 cells was characterized in an in vitro restitution model (scratch wound assay) with the help of time-lapse video microscopy, morphometry, and immunocytochemistry including confocal laser scanning microscopy. Results: TFF3- and EGF-treated cells re-populated the wounded area via different migration patterns; TFF3 treatment resulted in the formation of continuous sheets of migrating cells with only a few gaps. In contrast, EGF-treated cells formed a network of migrating cells (often with a fibroblast-like morphology) with numerous gaps and only punctual contacts. TFF3 and EGF treatment also changed the localization of E-cadherin indicating endocytotic recycling and/or degradation of E-cadherin. Conclusion: TFF3, in contrast to EGF, enhanced a collective cell migration ensuring a precise coverage of the re-populated area avoiding gaps.

Regulatory Function of Trefoil peptides (TFF) on Intestinal Cell Junctional Complexes

“…At fi rst glance our fi ndings of an increased extent of tight junction functions after TFF3 stimulation may appear in contradiction with the disruption of the E-cadherin/catenin complex and the reduced E-cadherin membranous expression described previously (Liu et al, 1997;Meyer zum Buschenfelde et al, 2004;D ü rer et al, 2007). However, two models for how E-cadherin adhesion can control tight junction formation have been proposed.…”

Milk Fat Globule-Epidermal Growth Factor 8 Is Decreased in Intestinal Epithelium of Ulcerative Colitis Patients and Thereby Causes Increased Apoptosis and Impaired Wound Healing

“…It is a protease-resistant peptide secreted by goblet cells of the small intestine and colon that can promote IEC migration and intestinal restitution through a mechanism independent of TGF-β1 (35)(36)(37). Colonic TFF3 expression was found reduced in trinitro-benzene-sulfonic acid-induced rat colitis (38).…”

E-cadherin Is Critical for Collective Sheet Migration and Is Regulated by the Chemokine CXCL12 Protein During Restitution

“…Trefoil factor family 3 also evokes collective cell migration, whereas EGF-treated cells migrate individually like fibroblasts (32). Thus, to test the hypothesis that CXCL12 and TGF-␤1 stimulation induce distinct migration phenotypes, the number and area of the space between cells were quantified.…”