Role of AKT/PKB signaling in fibroblast growth factor‐1 (FGF‐1)‐induced angiogenesis in the chicken chorioallantoic membrane (CAM)

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Abstract
Transfection of chicken chorioallantoic membranes (CAMs) with a chimeric secreted version of fibroblast growth factor‐1 (sp‐FGF‐1) gene construct leads to a significant increase in vascularization. Though FGF‐stimulated angiogenesis has been extensively studied, the molecular mechanisms regulating FGF‐1‐induced angiogenesis are poorly understood in vivo. This study was designed to investigate the role of the AKT (PKB) kinase signaling pathway in mediating sp‐FGF‐1‐induced angiogenesis in the chicken CAM. The involvement of the AKT pathway was demonstrated by up‐regulation of AKT1 mRNA expression in sp‐FGF‐1 compared to vector alone control transfected CAMs as demonstrated by real‐time RT‐PCR. Western analysis using an antibody specific to the activated AKT (phosphorylated AKT), demonstrated an increase in AKT activity in sp‐FGF‐1 compared to vector control transfected CAMs. More importantly, the AKT inhibitor ML‐9 significantly reduced sp‐FGF‐1‐induced angiogenesis in CAMs. These results indicate that AKT signaling plays a role in FGF‐1‐stimulated angiogenesis in vivo and the AKT pathway may serve as a therapeutic target for angiogenesis‐associated diseases.

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