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Effects of Histone Deacetylase Inhibitor (Valproic Acid) on the Expression of Hypoxia-inducible Factor-1 Alpha in Human Retinal Müller Cells

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Purpose: To evaluate the effects of valproic acid (VPA), a histone deacetylase inhibitor (HDACI), on the expressionof hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) in human retinalMüller cells under hypoxic conditions. Methods: Chemical hypoxia was induced in human retinal Müller cells (MIO-M1) by treatment with increasingconcentrations of cobalt(Ⅱ) chloride (CoCl2). Müller cells were also treated with a set concentration of CoCl2,along with various concentrations of VPA. The expression of HIF-1α and VEGF in the treated Müller cells wasdetermined by enzyme-linked immunosorbent assay. Results: Exposure of human retinal Müller cells to increasing concentrations of CoCl2 produced a dose-dependentincrease in HIF-1α expression. The addition of increasing concentrations of VPA lead to a dose-dependentdecrease in expression of HIF-1α and VEGF in Müller cells exposed to a set concentration of CoCl2. Conclusions: HDACI VPA downregulated the expressions of HIF-1α and VEGF in human retinal Müller cellsunder hypoxic conditions. Using HDACI to target HIF-1α expression in Müller cells could be a new therapeuticstrategy for the treatment of retinal vascular diseases.

Abstract

Purpose: To evaluate the effects of valproic acid (VPA), a histone deacetylase inhibitor (HDACI), on the expressionof hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) in human retinalMüller cells under hypoxic conditions. Methods: Chemical hypoxia was induced in human retinal Müller cells (MIO-M1) by treatment with increasingconcentrations of cobalt(Ⅱ) chloride (CoCl2). Müller cells were also treated with a set concentration of CoCl2,along with various concentrations of VPA. The expression of HIF-1α and VEGF in the treated Müller cells wasdetermined by enzyme-linked immunosorbent assay. Results: Exposure of human retinal Müller cells to increasing concentrations of CoCl2 produced a dose-dependentincrease in HIF-1α expression. The addition of increasing concentrations of VPA lead to a dose-dependentdecrease in expression of HIF-1α and VEGF in Müller cells exposed to a set concentration of CoCl2. Conclusions: HDACI VPA downregulated the expressions of HIF-1α and VEGF in human retinal Müller cellsunder hypoxic conditions. Using HDACI to target HIF-1α expression in Müller cells could be a new therapeuticstrategy for the treatment of retinal vascular diseases.

참고문헌 (47)

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