Mesenchymal stem cell migration is regulated by fibronectin through ?5?1-integrin-mediated activation of PDGFR-? and potentiation of growth factor signals.

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

SUBMITTER: Veevers-Lowe J 

PROVIDER: S-EPMC3065385 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature