α5β1 integrin activates an NF-κB-dependent program of gene expression important for angiogenesis and inflammation

GeneCalling, a genome-wide method of mRNA profiling, reveals that endothelial cells adhering to fibronectin through the alpha5beta1 integrin, but not to laminin through the alpha2beta1 integrin, undergo a complex program of gene expression. Several of the genes identified are regulated by the NF-kappaB transcription factor, and many are implicated in the regulation of inflammation and angiogenesis. Adhesion of endothelial cells to fibronectin activates NF-kappaB 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-kappaB, IkappaB-2A, blocks basic fibroblast growth factor-induced angiogenesis in vivo. These results suggest that engagement of the alpha5beta1 integrin promotes an NF-kappaB-dependent program of gene expression that coordinately regulates angiogenesis and inflammation.