Klein Sharon, de Fougerolles Antonin R, Blaikie Pamela, Khan Leila, Pepe Angela, Green Cynthia D, Koteliansky Victor, Giancotti Filippo G
Cellular Biochemistry and Biophysics Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Mol Cell Biol. 2002 Aug;22(16):5912-22. doi: 10.1128/MCB.22.16.5912-5922.2002.
GeneCalling, a genome-wide method of mRNA profiling, reveals that endothelial cells adhering to fibronectin through the alpha 5 beta 1 integrin, but not to laminin through the alpha 2 beta 1 integrin, undergo a complex program of gene expression. Several of the genes identified are regulated by the NF-kappa B transcription factor, and many are implicated in the regulation of inflammation and angiogenesis. Adhesion of endothelial cells to fibronectin activates NF-kappa B 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-kappa B, I kappa B-2A, blocks basic fibroblast growth factor-induced angiogenesis in vivo. These results suggest that engagement of the alpha 5 beta 1 integrin promotes an NF-kappa B-dependent program of gene expression that coordinately regulates angiogenesis and inflammation.
基因表达谱分析（GeneCalling）是一种全基因组范围的mRNA分析方法，该方法显示，内皮细胞通过α5β1整合素黏附于纤连蛋白，但不通过α2β1整合素黏附于层粘连蛋白，会经历一个复杂的基因表达程序。所鉴定出的几个基因受核因子κB（NF-κB）转录因子调控，且许多基因与炎症和血管生成的调控有关。内皮细胞与纤连蛋白的黏附通过一条需要Ras、磷脂酰肌醇3激酶和Rho家族蛋白的信号通路激活NF-κB，而与层粘连蛋白的黏附作用有限。NF-κB的超抑制剂IκB-2A的逆转录病毒转移可在体内阻断碱性成纤维细胞生长因子诱导的血管生成。这些结果表明，α5β1整合素的结合促进了一个依赖NF-κB的基因表达程序，该程序可协调调控血管生成和炎症。
