Modulation of Cell-cell Contacts during Intestinal Restitution In Vitro and Effects of Epidermal Growth Factor (EGF)

Abstract

Mucous epithelia represent a major barrier to the outside world and are capable of undergoing rapid repair after injury by cell migration, a process called “restitution”. Here, a sensitive RT-PCR method was applied allowing systematic gene expression analysis of separated stationary and migratory non-transformed IEC-18 and IEC-6 cells after scratch wounding. The focus was on genes related to cell-cell contacts. Furthermore, the effect of epidermal growth factor (EGF) on gene expression was studied. Most of the genes investigated here were down-regulated in migratory cells. Many of the alterations are expected to affect the permeability of tight junctions. Also the nectin-afadin complex of adherens junctions was modulated as well as the expression of both the chemokine receptor CXCR4 and the EGF receptor. Of note, restitution was not accompanied by the epithelial-mesenchymal transition (EMT). EGF treatment severely affected the expression of genes important for cell-cell contact and cell communication such as selected tight junction components, CXCR4, and TFF3. Many of these genes are known to be involved in EMT and metastasis. Of special note, most of the expression changes induced by EGF are in contrast to the changes observed in migratory cells.