Objective To investigate the up-regulation of VEGF
expression induced by long-term
hypoxia in ARPE-19 cells, the effects of genistein(Gen) on hypoxia-induced VEGF expression, and the mechanisms by which Gen worked. Methods RT-PCR and ELISA were performed to examine the
expressions of VEGF mRNA and protein when ARPE-19
cells were exposed to hypoxia for 24 hours, and different concentrations of Gen, PD98059 and Tyr-phostin A25 were used to observe their effects on the expressions. Results Hypoxia could up-regulate the expression of VEGF mRNA and protein(9.566± 1.528) times and (2. 636± 0. 499) times, respectively, as the normal control which showed little expression of VEGF; Gen inhibited the expression of VEGF mRNA induced by hypoxia for 24 hours in a dose-dependent manner, the inhibitory rate were 55.03% ,78.72% and 90.69% ,
respectively with the expressions of VEGF protein of(189. 60±20.20) ng·L-1, (117.70±21.97) ng·L-1.and (49.70±13.17) ng·L-1 respectively. PD98059 and Tyrphostin A25 could also inhibit the hypoxia-induced expression of VEGF mRNA by 67.24% and 56.25% , respectively,with the protein expressions of(86.33±12.47) ng·L-1 and(98.08±2.42) ng·L-1, respectively. Conclusion Gen could inhibit hypoxia-induced VEGF expression in ARPE-19 cells possibly through the inhibition of p42/ p44MAPK and HIF-1 pathways. It was suggested that Gen might play a latent role in the prevention and treatment of retinal neovascularization.
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