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Expression of Glutamate Receptor Subtype 3 Is Epigenetically Regulated in Podocytes under Diabetic Conditions.

ABSTRACT: Background: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. Methods: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. Results: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 (ESX1 and GRIA3) with decreased mRNA expression. Glutamate ionotropic receptor AMPA type subunit 3 (GRIA3) 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 GRIA3 expression and its function in podocytes. Real-time PCR and western blots confirmed the suppression of GRIA3 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 GRIA3 promoter region. GRIA3 mRNA and protein expression was suppressed in diabetic kidneys of human and mouse models, and knockdown of GRIA3 exacerbated high glucose-induced apoptosis in cultured podocytes. Conclusion:These results indicate that decreased GRIA3 expression in podocytes in diabetic condition heightens podocyte apoptosis and loss.

SUBMITTER: Li Z

PROVIDER: S-EPMC6388444 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Expression of Glutamate Receptor Subtype 3 Is Epigenetically Regulated in Podocytes under Diabetic Conditions.

Li Zhengzhe Z Chen Haibing H Zhong Fang F Zhang Weijia W Lee Kyung K He John Cijiang JC

Kidney diseases (Basel, Switzerland) 20181026 1

<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>Comparative analysis of genes with DNA methylation changes and corresponding ...[more]

PMID: 30815463

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Project description:BackgroundThe micropropagation is a powerful tool to scale up plants of economical and agronomical importance, enhancing crop productivity. However, a small but growing body of evidence suggests that epigenetic mechanisms, such as DNA methylation and histone modifications, can be affected under the in vitro conditions characteristic of micropropagation. Here, we tested whether the adaptation to different in vitro systems (Magenta boxes and Bioreactors) modified epigenetically different clones of Agave fourcroydes and A. angustifolia. Furthermore, we assessed whether these epigenetic changes affect the regulatory expression of KNOTTED1-like HOMEOBOX (KNOX) transcription factors.ResultsTo gain a better understanding of epigenetic changes during in vitro and ex vitro conditions in Agave fourcroydes and A. angustifolia, we analyzed global DNA methylation, as well as different histone modification marks, in two different systems: semisolid in Magenta boxes (M) and temporary immersion in modular Bioreactors (B). No significant difference was found in DNA methylation in A. fourcroydes grown in either M or B. However, when A. fourcroydes was compared with A. angustifolia, there was a two-fold difference in DNA methylation between the species, independent of the in vitro system used. Furthermore, we detected an absence or a low amount of the repressive mark H3K9me2 in ex vitro conditions in plants that were cultured earlier either in M or B. Moreover, the expression of AtqKNOX1 and AtqKNOX2, on A. fourcroydes and A. angustifolia clones, is affected during in vitro conditions. Therefore, we used Chromatin ImmunoPrecipitation (ChIP) to know whether these genes were epigenetically regulated. In the case of AtqKNOX1, the H3K4me3 and H3K9me2 were affected during in vitro conditions in comparison with AtqKNOX2.ConclusionsAgave clones plants with higher DNA methylation during in vitro conditions were better adapted to ex vitro conditions. In addition, A. fourcroydes and A. angustifolia clones displayed differential expression of the KNOX1 gene during in vitro conditions, which is epigenetically regulated by the H3K4me3 and H3K9me2 marks. The finding of an epigenetic regulation in key developmental genes will make it important in future studies to identify factors that help to find climate-resistant micropropagated plants.

Dataset Information

Expression of Glutamate Receptor Subtype 3 Is Epigenetically Regulated in Podocytes under Diabetic Conditions.

Publications

Expression of Glutamate Receptor Subtype 3 Is Epigenetically Regulated in Podocytes under Diabetic Conditions.

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