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목적 : The purpose of this study is to evaluate the effects of histone deacetylase inhibitor (valproic acid) on the expression of hypoxia inducible factor-α(HIF-α) and VEGF in human retinal muller cells under oxidative stress.
방법 : Human retinal muller cells (MIO-M1) were cultured in a humidified incubator at 378C in an atmosphere containing 95% air and 5% CO2.
Human retinal muller cells (MIO-M1) were treated with CoCl2 (100, 200, 300, 400, 500µM) and were measured of concentration of HIF-1α. And muller cells were devided into normoxia and hypoxia group.
Various concentrations (10, 25, 50, 75, 100µM) of histone deacetylase inhibitor (valproic acid) were treated in hypoxia and normoxia group.
ELISA was performed to evaluate the expression of HIF-1α and VEGF in human retinal muller cells.
결과 : 1. HIF-1α in human retinal muller cells were increased by increasing concentrations of CoCl2. Peak level of HIF-1α was detected in 400µM of CoCl2.
2. The hypoxic accumulation of HIF-1α was in duced by 400µM of CoCl2 which induced peak level of HIF-1α in Figure 1. In hypoxia group, HIF-1α in human retinal muller cells were increased than normoxia group. And HIF-1α decreased by increasing concentrations of valproic acid.
3. In hypoxia group, VEGF in human retinal muller cells were increased than normoxia group. And VEGF decreased by increasing concentrations of valproic acid.
결론 :
HDACIs have been actively explored as a new generation of chemotherapeutics for cancers. Recent findings indicated that several types of HDACIs repress angiogenesis by disrupting the function of hypoxia-inducible factors (HIF), which are the master regulators of angiogenesis and cellular adaptation to hypoxia.
Our result show valproic acid, one of the HDACIs, downregulate the expression of HIF-α in human retinal muller cells at hypoxia contidion and VEGF either. Targeting HIF-1α by HDACIs in Muller cells could be a new therapeutic strategy for the treatment of retinal vascular diseases.
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