Regulation of Vascular Endothelial Growth Factor Expression by Insulin-Like Growth Factor I

• DOI: 10.2337/diacare.46.10.1619
• Publication Date: 2013-09-19T17:42:54Z
• Authors: Rinaa S Punglia; Ming Lu; Julia Hsu; Masatoshi Kuroki; Michael J Tolentino; Karen Keough; Andrew P Levy; Nina S Levy; Mark A Goldberg; Robert J D'Amato; Anthony P Adamis
• Keywords: Lymphokines; 0303 health sciences; Endothelial Growth Factors; Blotting, Northern; Antibodies; Cell Hypoxia; Capillaries; Receptor, IGF Type 1; Kinetics; Mice; 03 medical and health sciences; Gene Expression Regulation; Culture Media, Conditioned; Animals; Humans; Endothelium, Vascular; RNA, Messenger; Insulin-Like Growth Factor I; Pigment Epithelium of Eye; Promoter Regions, Genetic; Cell Division; Cell Line, Transformed

Insulin-like growth factor I (IGF-I) and vascular endothelial (VEGF) levels are correlated with retinal ischemia-associated intraocular neovascu-larization in humans. Since VEGF is required for iris neovascularization animal models of ischemia, we tested whether IGF-I could act as an indirect angiogenic by increasing gene expression. increased pigment epithelial (RPE) cell mRNA a concentration-dependent manner EC50 7 nmol/l (53.6 ng/ml). RPE bovine smooth muscle cells exposed to 50 nmol/1 (383 ng/ml) achieved peak expression within 2 h. IGF-I-treated protein conditioned media stimulated capillary proliferation. Blockade the receptor neutralizing antibody abrogated increases cells. Further, hypoxia-mediated IGF-I-mediated were additive cells, hypoxia-induced independent endogenous IGF-I. promoter activity was enhanced but transcript half-life unaltered. In summary, supplementation cultures at 5-100 secreted levels. The occurred primarily through transcription via receptor. Elevated may promote