E-cadherin Is Critical for Collective Sheet Migration and Is Regulated by the Chemokine CXCL12 Protein During Restitution
- Resource Type
- Authors
- Kimberle A. Agle; Soonyean Hwang; Suresh Kumar; Michael B. Dwinell; Noah P. Zimmerman; Jerrold R. Turner
- Source
- Journal of Biological Chemistry. 287:22227-22240
- Subject
- Heterozygote
Chemokine
Biochemistry
Epithelium
Adherens junction
Intestinal mucosa
Cell Movement
Animals
Humans
Intestinal Mucosa
Molecular Biology
Wound Healing
Microscopy, Confocal
biology
Cadherin
Adherens Junctions
Cell Biology
Cadherins
Intestinal epithelium
Actins
Chemokine CXCL12
Recombinant Proteins
Rats
Cell biology
Restitution
Caco-2
Paracellular transport
biology.protein
Caco-2 Cells
Chemokines
Gene Deletion
- Language
- ISSN
- 0021-9258
Chemokines and other immune mediators enhance epithelial barrier repair. The intestinal barrier is established by highly regulated cell-cell contacts between epithelial cells. The goal of these studies was to define the role for the chemokine CXCL12 in regulating E-cadherin during collective sheet migration during epithelial restitution. Mechanisms regulating E-cadherin were investigated using Caco2(BBE) and IEC-6 model epithelia. Genetic knockdown confirmed a critical role for E-cadherin in in vitro restitution and in vivo wound repair. During restitution, both CXCL12 and TGF-β1 tightened the monolayer by decreasing the paracellular space between migrating epithelial cells. However, CXCL12 differed from TGF-β1 by stimulating the significant increase in E-cadherin membrane localization during restitution. Chemokine-stimulated relocalization of E-cadherin was paralleled by an increase in barrier integrity of polarized epithelium during restitution. CXCL12 activation of its cognate receptor CXCR4 stimulated E-cadherin localization and monolayer tightening through Rho-associated protein kinase activation and F-actin reorganization. These data demonstrate a key role for E-cadherin in intestinal epithelial restitution.