Faculty Collaboration Database

Rho activation regulates CXCL12 chemokine stimulated actin rearrangement and restitution in model intestinal epithelia. Lab Invest 2007 Aug;87(8):807-17

Date

06/19/2007

Pubmed ID

17572689

Pubmed Central ID

PMC2693067

DOI

10.1038/labinvest.3700595

Scopus ID

2-s2.0-34447534323 (requires institutional sign-in at Scopus site)   70 Citations

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.

Author List

Moyer RA, Wendt MK, Johanesen PA, Turner JR, Dwinell MB

Author

Michael B. Dwinell PhD Center Director, Professor in the Microbiology and Immunology department at Medical College of Wisconsin

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

Actins
Animals
Cell Line
Cell Line, Tumor
Cell Movement
Cell Polarity
Chemokine CXCL12
Chemokines, CXC
Enzyme Activation
Epithelial Cells
Humans
Intestinal Mucosa
Intracellular Signaling Peptides and Proteins
Myosin Light Chains
Phosphorylation
Rats
Receptors, CXCR4
rho GTP-Binding Proteins
rho-Associated Kinases