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- Title
Regulation of vascular endothelial growth factor expression by insulin-like growth factor I.
- Authors
Punglia, Rinaa S.; Ming Lu; Hsu, Julia; Kuroki, Masatoshi; Tolentino, Michael J.; Keough, Karen; Levy, Andrew P.; Levy, Nina S.; Goldberg, Mark A.; D'Amato, Robert J.; Adamis, Anthony P.; Punglia, R S; Lu, M; Hsu, J; Kuroki, M; Tolentino, M J; Keough, K; Levy, A P; Levy, N S; Goldberg, M A
- Abstract
Insulin-like growth factor I (IGF-I) and vascular endothelial growth factor (VEGF) levels are correlated with retinal ischemia-associated intraocular neovascularization in humans. Since VEGF is required for iris and retinal neovascularization in animal models of retinal ischemia, we tested whether IGF-I could act as an indirect angiogenic factor by increasing VEGF gene expression. IGF-I increased retinal pigment epithelial (RPE) cell VEGF mRNA in a concentration-dependent manner with an EC50 of 7 nmol/1 (53.6 ng/ml). RPE and bovine smooth muscle cells exposed to 50 nmol/l (383 ng/m1) IGF-I achieved peak VEGF mRNA expression within 2 h. IGF-I-treated RPE cells increased VEGF protein levels in conditioned media and stimulated capillary endothelial cell proliferation. Blockade of the IGF-I receptor with a neutralizing antibody abrogated the VEGF increases in RPE cells. Further, hypoxia-mediated and IGF-I-mediated increases in VEGF mRNA and protein levels were additive in RPE cells, and the hypoxia-induced VEGF increases were independent of endogenous IGF-I. VEGF promoter activity was enhanced by IGF-I in RPE cells, but VEGF transcript half-life was unaltered. In summary, the supplementation of RPE and smooth muscle cell cultures with IGF-I at 5-100 nmol/l increased VEGF mRNA and secreted protein levels. The VEGF increases in RPE cells occurred primarily through enhanced transcription of the VEGF gene and via the IGF-I receptor. Elevated IGF-I levels may promote neovascularization through increased retinal VEGF gene expression.
- Publication
Diabetes, 1997, Vol 46, Issue 10, p1619
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diacare.46.10.1619