Mesenchymal stem cell migration is regulated by fibronectin through α5β1-integrin-mediated activation of PDGFR-β and potentiation of growth factor signals

被引:186
作者
Veevers-Lowe, Jennifer [1 ]
Ball, Stephen G. [1 ]
Shuttleworth, Adrian [1 ]
Kielty, Cay M. [1 ]
机构
[1] Univ Manchester, Fac Life Sci, Wellcome Trust Ctr Cell Matrix Res, Manchester M13 9PT, Lancs, England
基金
英国医学研究理事会;
关键词
Platelet-derived growth factor receptor-beta; alpha; 5; beta; 1-Integrin; Fibronectin; Mesenchymal stem cell; Signalling; Migration; FACTOR RECEPTOR-BETA; BLOOD-VESSEL FORMATION; EGF-RECEPTOR; EXTRACELLULAR-MATRIX; BINDING-SITE; INTEGRIN; ACTIN; KINASE; PHOSPHORYLATION; ADHESION;
D O I
10.1242/jcs.076935
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:1288 / 1300
页数:13
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