Role of AKT/PKB signaling in fibroblast growth factor-1 (FGF-1)-induced angiogenesis in the chicken chorioallantoic membrane (CAM).
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.
Forough
Reza
R
Department of Medical Physiology and Cardiovascular Research Institute, College of Medicine, The Texas A&M University System Health Science Center, College Station, Texas 77843, USA. forough@tamu.edu
Weylie
Brian
B
Patel
Chirag
C
Ambrus
Sandy
S
Singh
Ugra S
US
Zhu
James
J
D000818:Animals; D001483:Base Sequence; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply*; D017931:DNA Primers; D016220:Fibroblast Growth Factor 1 / Q000235:genetics / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection
D017931:DNA Primers; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016220:Fibroblast Growth Factor 1; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt