ArticlePloS one2016
Hypoxia-Induced Changes in DNA Methylation Alter RASAL1 and TGFβ1 Expression in Human Trabecular Meshwork Cells.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 51 citations in OpenAlex.
- Erythropoiesis-inosine metabolic axis failure underlying retinal neurodegeneration in glaucoma: novel diagnoses and therapies.Experimental & molecular medicine · 2026Article
- Hypoxia regulates epithelial to mesenchymal transition-associated genes in human trophoblast cells by modulating DNA methylation.PloS one · 2026Article
- Epigenetics of glaucoma in the trabecular meshwork.Clinical epigenetics · 2025Review
- Recent Updates on Molecular and Physical Therapies for Organ Fibrosis.Molecules (Basel, Switzerland) · 2025Review
- Article
- Mendelian randomization implicates causal association between epigenetic age acceleration and age-related eye diseases or glaucoma endophenotypes.Clinical epigenetics · 2024Article
- Identification of Optic Nerve-Related Biomarkers in Primary Open-Angle Glaucoma Based on Comprehensive Bioinformatics and Mendelian Randomization.Translational vision science & technology · 2024Article
- Exploring Epigenetic Modifications as Potential Biomarkers and Therapeutic Targets in Glaucoma.International journal of molecular sciences · 2024Review
- Dysregulation of histone deacetylases in ocular diseases.Archives of pharmacal research · 2024Review
- Glaucoma: Novel antifibrotic therapeutics for the trabecular meshwork.European journal of pharmacology · 2023Review
- Pathophysiological mechanisms and therapeutic approaches in obstructive sleep apnea syndrome.Signal transduction and targeted therapy · 2023Review
- Epigenetics Approaches toward Precision Medicine for Idiopathic Pulmonary Fibrosis: Focus on DNA Methylation.Biomedicines · 2023Review
- Precision Medicine in Glaucoma: Artificial Intelligence, Biomarkers, Genetics and Redox State.International journal of molecular sciences · 2023Review
- Truncation mutations in MYRF underlie primary angle closure glaucoma.Human genetics · 2023Article
- The role of the adaptive immune system and T cell dysfunction in neurodegenerative diseases.Journal of neuroinflammation · 2022Review
- Association Between Diabetes, Diabetic Retinopathy, and Glaucoma.Current diabetes reports · 2021Review
- lnc-MAP3K13-7:1 Inhibits Ovarian GC Proliferation in PCOS via DNMT1 Downregulation-Mediated CDKN1A Promoter Hypomethylation.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Cutting Edge: Hypoxia-Induced Ubc9 Promoter Hypermethylation Regulates IL-17 Expression in Ulcerative Colitis.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Transforming Growth Factor-β1 Promotes M1 Alveolar Macrophage Polarization in Acute Lung Injury by Up-Regulating DNMT1 to Mediate the microRNA-124/PELI1/IRF5 Axis.Frontiers in cellular and infection microbiology · 2021Article
- Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeFibrosis and a hypoxic environment are associated with the trabecular meshwork (TM) region in the blinding disease glaucoma. Hypoxia has been shown to alter DNA methylation, an epigenetic mechanism involved in regulating gene expression such as the pro-fibrotic transforming growth factor (TGF) β1 and the anti-fibrotic Ras protein activator like 1 (RASAL1). The purpose of this study was to compare DNA methylation levels, and the expression of TGFβ1 and RASAL1 in primary human normal (NTM) with glaucomatous (GTM) cells and in NTM cells under hypoxic conditions.
methodsGlobal DNA methylation was assessed by ELISA in cultured age-matched NTM and GTM cells. qPCR was conducted for TGFβ1, collagen 1α1 (COL1A1), and RASAL1 expression. Western immunoblotting was used to determine protein expression. For hypoxia experiments, NTM cells were cultured in a 1%O2, 5%CO2 and 37°C environment. NTM and GTM cells were treated with TGFβ1 (10ng/ml) and the methylation inhibitor 5-azacytidine (5-aza) (0.5μM) respectively to determine their effects on DNA Methyltransferase 1 (DNMT1) and RASAL1 expression.
resultsWe found increased DNA methylation, increased TGFβ1 expression and decreased RASAL1 expression in GTM cells compared to NTM cells. Similar results were obtained in NTM cells under hypoxic conditions. TGFβ1 treatment increased DNMT1 and COL1A1, and decreased RASAL1 expression in NTM cells. 5-aza treatment decreased DNMT1, TGFβ1 and COL1A1 expression, and increased RASAL1 expression in GTM cells.
conclusionsTGFβ1 and RASAL1 expression, global DNA methylation, and expression of associated methylation enzymes were altered between NTM and GTM cells. We found that hypoxia in NTM cells induced similar results to the GTM cells. Furthermore, DNA methylation, TGFβ1 and RASAL1 appear to have an interacting relationship that may play a role in driving pro-fibrotic disease progression in the glaucomatous TM.
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