Chemokine stimulation promotes enterocyte migration through laminin-specific integrins. Am J Physiol Gastrointest Liver Physiol 2011 Dec;301(6):G968-80
Date
09/17/2011Pubmed ID
21921288Pubmed Central ID
PMC3233784DOI
10.1152/ajpgi.00208.2011Scopus ID
2-s2.0-82455219469 (requires institutional sign-in at Scopus site) 13 CitationsAbstract
Intestinal homeostasis is regulated in part by the single cell layer of the mucosal epithelium. This physical barrier is a prominent part of the innate immune system and possesses an intrinsic ability to heal damage and limit infection. The restitutive epithelial migration phase of healing requires dynamic integrin adhesion to the extracellular matrix. Previously, we have shown that the homeostatic chemokine CXCL12 utilizes intracellular calcium to increase enterocyte migration on laminin. The aim of these studies was to investigate integrin specificity and, in turn, functional responses elicited by CXCL12 stimulation. Analysis of cellular adhesion and spreading revealed CXCL12 preferentially activated laminin-specific integrins compared with collagen IV-binding integrins. Laminin-specific cell adhesion and spreading elicited by CXCL12 was dependent on intracellular calcium. CXCL12 increased activated β1-integrins on the surface of epithelial cells compared with untreated cells. RT-PCR confirmed expression of the laminin-binding integrins-α3β1, -α6β1, and -α6β4. Interestingly, shRNA-mediated depletion of laminin-specific α3- or α6-integrin subunits revealed differential functions. α3-Integrin knockdown reduced basal as well as inducible restitution. Depletion of α6-integrin specifically abolished CXCL12-stimulated, but not TGF-β1 or basal, migration. Depletion with either shα3-integrin or shα6-integrin prevented CXCL12-evoked cell spreading. Our data indicate that CXCL12 stimulates the inside-out activation of laminin-specific integrins to promote cell migratory functions. Together, our findings support the notion that extracellular mediators within the gastrointestinal mucosa coordinate cell-matrix interactions during epithelial restitution.
Author List
Agle KA, Vongsa RA, Dwinell MBAuthor
Michael B. Dwinell PhD Center Director, Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCaco-2 Cells
Calcium
Cell Adhesion
Cell Movement
Chemokine CXCL12
Enterocytes
Epithelial Cells
Extracellular Matrix
Humans
Integrin alpha3
Integrin alpha6
Integrin beta1
Integrin beta4
Intestinal Mucosa
Laminin
RNA, Small Interfering
Rats
Recombinant Proteins
