Abstract: |
GeneCalling, a genome-wide method of mRNA profiling, reveals that endothelial cells adhering to fibronectin through the α5β1 integrin, but not to laminin through the α2β1 integrin, undergo a complex program of gene expression. Several of the genes identified are regulated by the NF-κB transcription factor, and many are implicated in the regulation of inflammation and angiogenesis. Adhesion of endothelial cells to fibronectin activates NF-κB through a signaling pathway requiring Ras, phosphatidylinositol 3-kinase, and Rho family proteins, whereas adhesion to laminin has a limited effect. Retroviral transfer of the superrepressor of NF-κB, IκB-2A, blocks basic fibroblast growth factor-induced angiogenesis in vivo. These results suggest that engagement of the α5β1 integrin promotes an NF-κB-dependent program of gene expression that coordinately regulates angiogenesis and inflammation. |
Keywords: |
signal transduction; human cell; dna-binding proteins; cell proliferation; animals; mice; cells, cultured; gene expression profiling; cell maturation; basement membrane; inflammation; transcription factor; immunoglobulin enhancer binding protein; angiogenesis; endothelium cell; extracellular matrix; fibroblast growth factor 2; gene expression regulation; gene activation; recombinant fusion proteins; endothelium, vascular; mice, nude; rna, messenger; nf-kappa b; 1-phosphatidylinositol 3-kinase; collagen; reactive oxygen species; ras proteins; drug combinations; neovascularization, physiologic; cell adhesion; biocompatible materials; integrin; rho gtp-binding proteins; tissue repair; laminin; i-kappa b proteins; proteoglycans; fibronectins; messenger rna synthesis; humans; human; priority journal; article; receptors, fibronectin
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