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
05/03/2012Pubmed ID
22549778Pubmed Central ID
PMC3381184DOI
10.1074/jbc.M112.367979Scopus ID
2-s2.0-84862705745 (requires institutional sign-in at Scopus site) 38 CitationsAbstract
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 MBAuthors
Michael B. Dwinell PhD Director, Professor in the Microbiology and Immunology department at Medical College of WisconsinSuresh Kumar PhD Associate Professor in the Pathology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
ActinsAdherens 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
