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Chemokine stimulation promotes enterocyte migration through laminin-specific integrins
Kimberle A Agle1, Rebecca A Vongsa, Michael B Dwinell
1Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
American Journal of Physiology. Gastrointestinal and Liver Physiology
|September 17, 2011
Summary
The chemokine CXCL12 activates specific integrins in intestinal epithelial cells, promoting healing and migration. This process relies on intracellular calcium and involves laminin-binding integrins, crucial for barrier repair.
Area of Science:
- Gastrointestinal biology
- Cellular immunology
- Epithelial biology
Background:
- Intestinal homeostasis relies on the mucosal epithelium, a key physical barrier and innate immune component.
- Epithelial healing involves cell migration, requiring integrin adhesion to the extracellular matrix.
- The chemokine CXCL12 influences enterocyte migration via intracellular calcium.
Purpose of the Study:
- To investigate integrin specificity and functional responses to CXCL12 stimulation in intestinal epithelial cells.
- To determine the role of specific integrin subunits in CXCL12-mediated cell migration and spreading.
- To elucidate the mechanism of CXCL12-induced integrin activation.
Main Methods:
- Cellular adhesion and spreading assays.
- RT-PCR to confirm integrin expression.
- shRNA-mediated depletion of specific integrin subunits (α3 and α6).
- Analysis of cell migration and spreading in response to CXCL12 and TGF-β1.
Main Results:
- CXCL12 preferentially activated laminin-specific integrins over collagen IV-binding integrins.
- CXCL12-induced adhesion and spreading were calcium-dependent.
- Depletion of α3-integrin reduced basal and inducible restitution; α6-integrin depletion abolished CXCL12-stimulated migration.
- Both α3- and α6-integrin depletion prevented CXCL12-evoked cell spreading.
Conclusions:
- CXCL12 stimulates the inside-out activation of laminin-specific integrins, promoting epithelial cell migration.
- Specific integrins (α3β1, α6β1, α6β4) play distinct roles in epithelial restitution.
- Extracellular mediators like CXCL12 coordinate cell-matrix interactions for gastrointestinal mucosal healing.
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