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• W2898092523 abstract "<b><i>Background:</i></b> Recent studies suggest a role of epigenetics in the pathogenesis of diabetic kidney disease. However, epigenetic changes occurring specifically in kidney cells is poorly understood. <b><i>Methods:</i></b> To examine the epigenetic regulation of genes in podocytes under diabetic conditions, we performed DNA methylation and transcriptomic profiling in podocytes exposed to high glucose conditions. <b><i>Results:</i></b> Comparative analysis of genes with DNA methylation changes and correspondingly altered mRNA expression identified 337 hypomethylated genes with increased mRNA expression and only 2 hypermethyated genes (<i>ESX1</i> and<i> GRIA3</i>) with decreased mRNA expression. Glutamate ionotropic receptor AMPA type subunit 3 (<i>GRIA3</i>) belongs to the ionotropic class of glutamate receptors that mediate fast excitatory synaptic transmission in the central nervous system. As podocytes have glutamate-containing vesicles and various glutamate receptors mediate important biological effects in podocytes, we further examined <i>GRIA3</i> expression and its function in podocytes. Real-time PCR and western blots confirmed the suppression of <i>GRIA3</i> expression in podocytes under high glucose conditions, which were abolished in the presence of a DNA methyltransferase inhibitor. Sites of DNA hypermethylation were also confirmed by bisulfite sequencing of the <i>GRIA3</i> promoter region. <i>GRIA3</i> mRNA and protein expression was suppressed in diabetic kidneys of human and mouse models, and knockdown of <i>GRIA3</i> exacerbated high glucose-induced apoptosis in cultured podocytes. <b><i>Conclusion:</i></b> These results indicate that decreased <i>GRIA3</i> expression in podocytes in diabetic condition heightens podocyte apoptosis and loss." @default.
• W2898092523 created "2018-11-02" @default.
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• W2898092523 date "2018-10-26" @default.
• W2898092523 modified "2023-09-26" @default.
• W2898092523 title "Expression of Glutamate Receptor Subtype 3 Is Epigenetically Regulated in Podocytes under Diabetic Conditions" @default.
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• W2898092523 doi "https://doi.org/10.1159/000492933" @default.
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