title: E-cadherin is critical for collective sheet migration and is regulated by the chemokine CXCL12 protein during restitution.
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.
authors.affiliation: Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
authors.forename: Soonyean
authors.initials: S
authors.lastname: Hwang
authors.forename: Noah P
authors.initials: NP
authors.lastname: Zimmerman
authors.forename: Kimberle A
authors.initials: KA
authors.lastname: Agle
authors.forename: Jerrold R
authors.initials: JR
authors.lastname: Turner
authors.forename: Suresh N
authors.initials: SN
authors.lastname: Kumar
authors.forename: Michael B
authors.initials: MB
authors.lastname: Dwinell
mesh_terms: D000199:Actins / Q000378:metabolism; D022005:Adherens Junctions / Q000378:metabolism; D000818:Animals; D018938:Caco-2 Cells; D015820:Cadherins / Q000378:metabolism*; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000378:metabolism*; D018925:Chemokines / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D017353:Gene Deletion; D006579:Heterozygote; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D018613:Microscopy, Confocal / Q000379:methods; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D014945:Wound Healing
chemical_list: D000199:Actins; D015820:Cadherins; D054377:Chemokine CXCL12; D018925:Chemokines; D011994:Recombinant Proteins