Calcium Mobilization Triggered by the Chemokine CXCL12 Regulates Migration in Wounded Intestinal Epithelial Monolayers
作者： Kimberle A. Agle , Rebecca A. Vongsa , Michael B. Dwinell
关键词: Paxillin 、 Calcium signaling 、 Actin cytoskeleton 、 Epithelial cell migration 、 Chemokine receptor 、 Calcium in biology 、 Calcium 、 Biology 、 Cell biology 、 Focal adhesion
摘要: Restitution of intestinal epithelial barrier damage involves the coordinated remodeling focal adhesions in actively migrating enterocytes. Defining extracellular mediators and intracellular signaling pathways regulating those dynamic processes is a key step developing restitution-targeted therapies. Previously we have determined that activation chemokine receptor CXCR4 by cognate ligand CXCL12 enhances restitution through reorganization actin cytoskeleton. The aim these studies was to investigate role calcium effectors CXCL12-mediated restitution. stimulated release dose-dependent manner. Inhibition flux impaired migration IEC-6 CaCo2 cells. Pharmacological blockade specific shRNA depletion phospholipase-C (PLCβ3) isoform attenuated CXCL12-enhanced migration, linking with flux. Immunoblot analyses demonstrated activated calcium-regulated adhesion protein proline-rich tyrosine kinase-2 (Pyk2) effector proteins paxillin p130Cas. Interruption Pyk2 potently blocked CXCL12-induced wound closure. CXCL12-stimulated cell enhanced on laminin abrogated chelation. These results suggest regulates calcium-activated localized active adhesions. Calcium may therefore provide novel avenue for enhancing repair.
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