ArticleJournal of molecular endocrinology2015
Endothelial glucocorticoid receptor promoter methylation according to dexamethasone sensitivity.
Article in Journal of molecular endocrinology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- DNA methylation is associated with inhaled corticosteroid response in persistent childhood asthmatics.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2019Trial
- Decreased Glucocorticoid Receptor Expression and Function in Cord Blood Immune Cells from Preterm Neonates with Morbidity.International journal of molecular sciences · 2025Article
- Perinatal glucocorticoid sensitivity in the preterm newborn: molecular mechanisms, endogenous determinants, and clinical implications.Frontiers in endocrinology · 2025Review
- Convergence of endothelial dysfunction, inflammation and glucocorticoid resistance in depression-related cardiovascular diseases.BMC immunology · 2024Review
- Dysregulation of Glucocorticoid Receptor Homeostasis and Glucocorticoid-Associated Genes in Umbilical Cord Endothelial Cells of Diet-Induced Obese Pregnant Sheep.International journal of molecular sciences · 2024Article
- Antenatal Steroids and Cord Blood T-cell Glucocorticoid Receptor DNA Methylation and Exon 1 Splicing.Reproductive sciences (Thousand Oaks, Calif.) · 2022Article
- Role of Endothelial Glucocorticoid Receptor in the Pathogenesis of Kidney Diseases.International journal of molecular sciences · 2021Review
- The Role of Epigenetics in the Chronic Sinusitis with Nasal Polyp.Current allergy and asthma reports · 2020Review
- Psychosocial Stress, Glucocorticoid Signaling, and Prostate Cancer Health Disparities in African American Men.Cancer health disparities · 2020Article
- Glucocorticoids and programming of the microenvironment in heart.The Journal of endocrinology · 2019Review
- [Effects of icariin on autophagy and exosome production of bone microvascular endothelial cells].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2019Article
- DNA methylation is associated with improvement in lung function on inhaled corticosteroids in pediatric asthmatics.Pharmacogenetics and genomics · 2019Article
- Article
- Vitamin D status and metabolism in an ovine pregnancy model: effect of long-term, high-altitude hypoxia.American journal of physiology. Endocrinology and metabolism · 2016Article
- Antenatal hypoxia induces epigenetic repression of glucocorticoid receptor and promotes ischemic-sensitive phenotype in the developing heart.Journal of molecular and cellular cardiology · 2016Article
- Endothelial Response to Glucocorticoids in Inflammatory Diseases.Frontiers in immunology · 2016Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
We have previously shown that in vitro sensitivity to dexamethasone (DEX) stimulation in human endothelial cells is positively regulated by the glucocorticoid receptor (NR3C1, GR). The present study determined the role of differential GR transcriptional regulation in glucocorticoid sensitivity. We studied 25 human umbilical vein endothelial cells (HUVECs) that had been previously characterized as DEX-sensitive (n=15), or resistant (n=10). Real-time PCR analysis of GR 5'UTR mRNA isoforms showed that all HUVECs expressed isoforms 1B, 1C, 1D, 1F, and 1H, and isoforms 1B and 1C were predominantly expressed. DEX-resistant cells expressed higher basal levels of the 5'UTR mRNA isoforms 1C and 1D, but lower levels of the 5'UTR mRNA isoform 1F than DEX-sensitive cells. DEX treatment significantly decreased GRα and GR-1C mRNA isoform expression in DEX-resistant cells only. Reporter luciferase assays indicated that differential GR mRNA isoform expression was not due to differential promoter usage between DEX-sensitive and DEX-resistant cells. Analysis of promoter methylation, however, showed that DEX-sensitive cells have higher methylation levels of promoter 1D and lower methylation levels of promoter 1F than DEX-resistant cells. Treatment with 5-aza-2-deoxycytidine abolished the differential 5'UTR mRNA isoform expression between DEX-sensitive and DEX-resistant cells. Finally, both GRα overexpression and 5-aza-2-deoxycytidine treatment eliminated the differences between sensitivity groups to DEX-mediated downregulation of endothelial nitric oxide synthase (NOS3), and upregulation of plasminogen activator inhibitor 1 (SERPINE1). In sum, human endothelial GR 5'UTR mRNA expression is regulated by promoter methylation with DEX-sensitive and DEX-resistant cells having different GR promoter methylation patterns.
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