ArticleInvestigative ophthalmology & visual science2017
Crosstalk Between Histone and DNA Methylation in Regulation of Retinal Matrix Metalloproteinase-9 in Diabetes.
Article in Investigative ophthalmology & visual science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 65 citations in OpenAlex.
- Neonatal Sevoflurane Exposure Induces Long-Term Cognitive Impairment via Epigenetically Mediated MMP9 Activation and Perineuronal Net Disruption in the Hippocampal CA2.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Beyond hyperglycemia: histone modification-mediated epigenetic dysregulation in diabetic retinopathy and nephropathy.Diabetology & metabolic syndrome · 2026Review
- Diabetic keratopathy and nuclear proteins (Review).Molecular medicine reports · 2026Review
- ISDH-seq: a robust methodology for profiling and characterization of open chromatin.Plant biotechnology journal · 2025Article
- Applications of Matrix Metalloproteinase-9-Related Nanomedicines in Tumors and Vascular Diseases.Pharmaceutics · 2025Review
- The role and mechanisms of matrix metalloproteinase-9 in peripheral neuropathic pain.Frontiers in molecular neuroscience · 2025Review
- Repressive H3K27me3 drives hyperglycemia-induced oxidative and inflammatory transcriptional programs in human endothelium.Cardiovascular diabetology · 2024Article
- Coregulatory effects of multiple histone modifications in key ferroptosis-related genes for lung adenocarcinoma.Epigenomics · 2024Article
- TET2 mutation as prototypic clonal hematopoiesis lesion.Seminars in hematology · 2024Review
- Roles of MMP-2 and MMP-9 and their associated molecules in the pathogenesis of keloids: a comprehensive review.Frontiers in pharmacology · 2024Review
- Coenzyme Q10 eyedrops conjugated with vitamin E TPGS alleviate neurodegeneration and mitochondrial dysfunction in the diabetic mouse retina.Frontiers in cellular neuroscience · 2024Article
- The Role of Genetics and Epigenetic Regulation in the Pathogenesis of Osteoarthritis.International journal of molecular sciences · 2023Review
- The role of TET2-mediated ROBO4 hypomethylation in the development of diabetic retinopathy.Journal of translational medicine · 2023Article
- Diabetic Retinopathy and Cardiovascular Disease: A Literature Review.Diabetes, metabolic syndrome and obesity : targets and therapy · 2023Review
- DNA methylation in diabetic retinopathy: pathogenetic role and potential therapeutic targets.Cell & bioscience · 2022Review
- Depletion of miR-96 Delays, But Does Not Arrest, Photoreceptor Development in Mice.Investigative ophthalmology & visual science · 2022Article
- Leukocyte subtypes, gelatinases, and their tissue inhibitors in a group of subjects with asymptomatic carotid atherosclerosis.Clinical hemorheology and microcirculation · 2022Article
- Epigenetic modifications in diabetes.Metabolism: clinical and experimental · 2022Review
- Long Noncoding RNAs and Mitochondrial Homeostasis in the Development of Diabetic Retinopathy.Frontiers in endocrinology · 2022Review
- Epigenetic regulation of inflammatory factors in adipose tissue.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2021Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Purpose: Diabetes activates matrix metalloproteinase-9 (MMP-9), and MMP-9 via damaging retinal mitochondria, activates capillary cell apoptosis. MMP-9 promoter has binding sites for many transcription factors, and in diabetes its promoter undergoes epigenetic modifications, including histone modifications and DNA methylation. Enhancer of Zeste homolog 2 (Ezh2), which catalyzes dimethylation/trimethylation of histone 3 lysine 27 (H3K27me2 and me3), is also associated with DNA methylation. Our aim was to investigate link(s) between histone and DNA modifications in the regulation of MMP-9. Methods: Using human retinal endothelial cells, and also retinal microvessels from diabetic rats, effect of hyperglycemia on H3K27me3, and recruitment of Ezh2 at the MMP-9 promoter were quantified by chromatin-immunoprecipitation technique. Role of H3K27 trimethylation in regulating DNA methylation-transcription of MMP-9 was determined by regulating Ezh2 by its specific siRNA and also a pharmacologic inhibitor. Results: Hyperglycemia elevated H3K27me3 levels and the recruitment of Ezh2 at the MMP-9 promoter, and increased the enzyme activity of Ezh2. Inhibition of Ezh2 attenuated recruitment of both DNA methylating (Dnmt1) and hydroxymethylating (Tet2) enzymes and 5 hydroxymethyl cytosine at the same region of the MMP-9 promoter, and prevented increase in MMP-9 transcription and mitochondrial damage. Conclusions: Activation of Ezh2 in diabetes, via trimethylation of H3K27, facilitates recruitment of the enzymes responsible for regulation of DNA methylation of the MMP-9 promoter, resulting in its transcriptional activation. Thus, a close crosstalk between H3K27 trimethylation and DNA methylation in diabetes plays a critical role in the maintenance of cellular epigenetic integrity of MMP-9.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.