Rho activation regulates CXCL12 chemokine stimulated actin rearrangement and restitution in model intestinal epithelia

Rebecca A Moyer; Michael K Wendt; Priscilla A Johanesen; Jerrold R Turner; Michael B Dwinell

doi:10.1038/labinvest.3700595

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Rho activation regulates CXCL12 chemokine stimulated actin rearrangement and restitution in model intestinal epithelia

Journal article

Open access

Peer reviewed

Rho activation regulates CXCL12 chemokine stimulated actin rearrangement and restitution in model intestinal epithelia

Rebecca A Moyer, Michael K Wendt, Priscilla A Johanesen, Jerrold R Turner and Michael B Dwinell

Laboratory investigation, Vol.87(8), pp.807-817

08/01/2007

DOI: 10.1038/labinvest.3700595

PMCID: PMC2693067

PMID: 17572689

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Abstract

Chemokines are critical regulatory factors that direct migration, proliferation and maturation of receptor expressing target cells within gut mucosa. The aim of the present study was to define the cellular mechanisms whereby engagement of the essential chemokine CXCL12 to CXCR4 regulates restitutive epithelial cell migration. Non-transformed IEC-6 cells or polarized T84 epithelial monolayers were wounded and F-actin accumulation assessed using fluorescence microscopy and flow cytometry. Immunoblot analysis, pull-down assays, fluorescence microscopy and wound healing assays defined activation of Rho, Rho-kinase (ROCK), and myosin light chain (MLC) and the role for those Rho effectors in CXCL12-regulated epithelial restitution. CXCL12 increased RhoGTP and F-actin localization to the leading edge of wounded IEC-6 and T84 monolayers. CXCL12 congruently stimulated an increase in active MLC that was inhibited by blockade of ROCK and myosin light chain kinase and regulated epithelial migration. Our data in model intestinal epithelia suggest CXCR4 and CXCL12 may function as an autocrine and paracrine mucosal signaling network regulating the competency of the epithelial barrier to withstand injury and mediate repair following damage.

chemokines

epithelial cell migration

restitution

RhoGTPase

wound healing

Details

Title: Subtitle: Rho activation regulates CXCL12 chemokine stimulated actin rearrangement and restitution in model intestinal epithelia
Creators: Rebecca A Moyer - Medical College of Wisconsin
Michael K Wendt - Medical College of Wisconsin
Priscilla A Johanesen - Medical College of Wisconsin
Jerrold R Turner - University of Chicago
Michael B Dwinell - Medical College of Wisconsin
Resource Type: Journal article
Publication Details: Laboratory investigation, Vol.87(8), pp.807-817
Publisher: Elsevier Inc
DOI: 10.1038/labinvest.3700595
PMID: 17572689
PMCID: PMC2693067
ISSN: 0023-6837
eISSN: 1530-0307
Language: English
Date published: 08/01/2007
Academic Unit: Internal Medicine
Record Identifier: 9984460335302771

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