Targeting of αv integrins interferes with FAK activation and smooth muscle cell migration and invasion
Copyright policy )Targeting of αv integrins interferes with FAK activation and smooth muscle cell migration and invasion
Aberrant migration of smooth muscle cells (SMCs) is a key feature of restenosis. Since extracellular matrix proteins and their receptors of the integrin family play a critical role in this process, it is instrumental to understand their contribution to cell migration and invasive motility of SMC on the molecular level. Therefore, we investigated the role of alpha(v)-containing integrins expressed by primary human coronary artery smooth muscle cells (hCASMCs) in vitronectin (VN)-initiated signaling events and cell migration. In hCASMC plated on VN, alpha(v)-containing integrins were localized at focal adhesion sites. Haptotactic stimulation through VN led to a dose-dependent increase in cell migration and concomitantly to enhanced tyrosine phosphorylation of focal adhesion kinase. Both events were completely blocked by a specific inhibitor of integrin alpha(v). Additionally, the integrin alpha(v) inhibitor abolished PDGF-BB-stimulated chemotactic migration. Confocal microscopy confirmed the increased tyrosine phosphorylation at VN-initiated focal contact sites in hCASMC, that was abolished upon alpha(v) inhibition. In vitro invasion of hCASMC was severely compromised in the presence of the integrin alpha(v) inhibitor paralleled by decreased levels of secreted matrix metalloprotease 2 (MMP-2). Together, integrin alpha(v) inhibition abrogates tyrosine phosphorylation at focal adhesion sites and diminishes MMP-2 secretion leading to reduced migration and invasion of hCASMCs.
- University of Konstanz Germany
- University of Würzburg Germany
info:eu-repo/classification/ddc/570, Focal Adhesions, Myocytes, Smooth Muscle, Cell adhesion, Integrin alphaV, Protein-Tyrosine Kinases, Coronary Vessels, Substrate Specificity, Tyrosine phosphorylation, Enzyme Activation, Extracellular matrix proteins, Cell Movement, Focal Adhesion Kinase 1, Focal Adhesion Protein-Tyrosine Kinases, Humans, Vitronectin, Phosphorylation, Signal Transduction
info:eu-repo/classification/ddc/570, Focal Adhesions, Myocytes, Smooth Muscle, Cell adhesion, Integrin alphaV, Protein-Tyrosine Kinases, Coronary Vessels, Substrate Specificity, Tyrosine phosphorylation, Enzyme Activation, Extracellular matrix proteins, Cell Movement, Focal Adhesion Kinase 1, Focal Adhesion Protein-Tyrosine Kinases, Humans, Vitronectin, Phosphorylation, Signal Transduction
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).26 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Average influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!