Mesenchymal stem cell migration is regulated by fibronectin through α5β1-integrin-mediated activation of PDGFR-β 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)-beta and alpha 5 beta 1-integrin, which controls the migration of mesenchymal stem (stromal) cells (MSCs). Cell adhesion to fibronectin induced alpha 5 beta 1-integrin-dependent phosphorylation of PDGFR-beta in the absence of growth factor stimulation. Phosphorylated PDGFR-beta co-immunoprecipitated with alpha 5-integrin and colocalised with alpha 5 beta 1-integrin in the transient tidemarks of focal adhesions. Adhesion to fibronectin also strongly potentiated PDGF-BB-induced PDGFR-beta phosphorylation and focal adhesion kinase (FAK) activity, in an a5b1-integrin-dependent manner. PDGFR-beta-induced phosphoinositide 3-kinase (PI3K) and Akt activity, actin reorganisation and cell migration were all regulated by fibronectin and alpha 5 beta 1-integrin. This synergistic relationship between alpha 5 beta 1-integrin and PDGFR-beta is a fundamental determinant of cell migration. Thus, fibronectin-rich matrices can prime PDGFR-beta to recruit mesenchymal cells at sites of vascular remodelling.