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E-cadherin is critical for collective sheet migration and is regulated by the chemokine CXCL12 protein during restitution. J Biol Chem 2012 Jun 22;287(26):22227-40

Date

05/03/2012

Pubmed ID

22549778

Pubmed Central ID

PMC3381184

DOI

10.1074/jbc.M112.367979

Scopus ID

2-s2.0-84862705745   26 Citations

Abstract

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.

Author List

Hwang S, Zimmerman NP, Agle KA, Turner JR, Kumar SN, Dwinell MB

Authors

Michael B. Dwinell PhD Director, Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Suresh Kumar PhD Associate Professor in the Pathology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Actins
Adherens Junctions
Animals
Caco-2 Cells
Cadherins
Cell Movement
Chemokine CXCL12
Chemokines
Epithelium
Gene Deletion
Heterozygote
Humans
Intestinal Mucosa
Microscopy, Confocal
Rats
Recombinant Proteins
Wound Healing
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a