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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.
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页码:1288 / 1300
页数:13
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