Mesenchymal stem cell migration is regulated by fibronectin through α5ß1-integrin-mediated activation of PDGFR-ß and potentiation of growth factor signals.

Cell migration during vascular remodelling is regulated by crosstalk between growth factor receptors and integrin receptors, which together coordinate cytoskeletal and motogenic changes. Here, we report extracellular matrix (ECM)-directed crosstalk between platelet-derived growth factor receptor (PDGFR)-ß and α5ß1-integrin, which controls the migration of mesenchymal stem (stromal) cells (MSCs). Cell adhesion to fibronectin induced α5ß1-integrin-dependent phosphorylation of PDGFR-ß in the absence of growth factor stimulation. Phosphorylated PDGFR-ß co-immunoprecipitated with α5-integrin and colocalised with α5ß1-integrin in the transient tidemarks of focal adhesions. Adhesion to fibronectin also strongly potentiated PDGF-BB-induced PDGFR-ß phosphorylation and focal adhesion kinase (FAK) activity, in an α5ß1-integrin-dependent manner. PDGFR-ß-induced phosphoinositide 3-kinase (PI3K) and Akt activity, actin reorganisation and cell migration were all regulated by fibronectin and α5ß1-integrin. This synergistic relationship between α5ß1-integrin and PDGFR-ß is a fundamental determinant of cell migration. Thus, fibronectin-rich matrices can prime PDGFR-ß to recruit mesenchymal cells at sites of vascular remodelling.