HIF-1 is required for IGF-1-induced VEGF mRNA expression and protein secretion. HIF-1 is required for IGF-1-induced VEGF mRNA expression and protein secretion. A, Control, HIF-1α-DN- or HIF-1α-CA-expressing hippocampal neuron cultures were stimulated IGF-1 (300 ng/ml) for 6 h with or without echinomycin (0.5 μm). Levels of VEGF-A mRNA expression were analyzed by quantitative real-time PCR. B, VEGF-A mRNA levels were determined in control shRNA-DsRed, HIF-1α-shRNA-I-, or HIF-1α-shRNA-II-expressing hippocampal neuron cultures with or without IGF-1 (300 ng/ml) treatment for 6 h. C, Control, HIF-1α-DN-, or HIF-1α-CA-expressing hippocampal neuron cultures were stimulated IGF-1 (300 ng/ml) for 6 h with or without echinomycin (0.5 μm). Levels of VEGF-A protein secretion were determined by ELISA of the culture media. D, Secreted VEGF-A protein levels were determined in the culture media from control shRNA-DsRed, HIF-1α-shRNA-I-, or HIF-1α-shRNA-II-expressing hippocampal neuron cultures with or without IGF-1 (300 ng/ml) treatment for 6 h. Data are presented as mean ± SEM. *p < 0.05 compared with the vehicle (0.1% DMSO)-treated control group by unpaired Student's t test. Yu-Fei Huang et al. J. Neurosci. 2010;30:6080-6093 ©2010 by Society for Neuroscience