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  • Title: Triamcinolone acetonide destabilizes VEGF mRNA in Müller cells under continuous cobalt stimulation.
    Author: Sears JE, Hoppe G.
    Journal: Invest Ophthalmol Vis Sci; 2005 Nov; 46(11):4336-41. PubMed ID: 16249516.
    Abstract:
    PURPOSE: To identify the molecular mechanism of steroid-induced downregulation of vascular endothelial growth factor (VEGF) synthesis in Müller cells. METHODS: Confluent cultures of human Müller cells (MIO-M1) were treated with 100 microM CoCl(2), 1 microg/mL triamcinolone acetonide (TA), or both. VEGF secretion was measured with respect to time by ELISA. VEGF mRNA quantity and stability were analyzed by reverse transcriptase-polymerase chain reaction. The activity of hypoxia-inducible factor (HIF)-1 was measured by the relative binding of HIF-1 protein to the hypoxia response element (HRE), by gel shift and ELISA. The HIF-1alpha protein level was determined with Western blot. RESULTS: TA decreased VEGF secretion by at least 50% in the presence of continuous cobalt stimulus. VEGF mRNA decreased 50- to 100-fold 6 hours after treatment with TA and cobalt compared with cobalt alone. VEGF mRNA stability was decreased in cobalt-stimulated, TA-treated cells compared with cobalt alone in cells synchronized by exposure to actinomycin D. HIF-1alpha protein level was sustained for the entire 24-hour treatment period and partitioned into nuclear, not cytosolic, fractions. HIF-1 activity was decreased by 20% to 30% in the presence of TA and cobalt compared with cobalt alone. CONCLUSIONS: TA may decrease VEGF synthesis by nongenomic destabilization of VEGF mRNA in cobalt-stimulated Müller cells. There was little effect on the total HIF-1alpha protein level, HIF-1 partitioning, and HIF-1 activity.
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