α5β1 Integrin Activates an NF-κB-Dependent Program of Gene Expression Important for Angiogenesis and Inflammation

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.