ArticleLaboratory investigation; a journal of technical methods and pathology2016
Dynamic DNA methylation of matrix metalloproteinase-9 in the development of diabetic retinopathy.
Article in Laboratory investigation; a journal of technical methods and pathology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 120 citations in OpenAlex.
- Insulin Resistance and Inflammation.International journal of molecular sciences · 2026Review
- SARS-CoV-2 altered mitochondrial DNA methylation in Indian COVID-19 patients.Scientific reports · 2026Article
- Neurovascular unit uncoupling in diabetic retinopathy: molecular mechanisms and stage-adapted therapeutic strategies.Frontiers in endocrinology · 2026Review
- Activation of farnesoid X receptor upregulates binding immunoglobulin protein expression and alleviates diabetic nephropathy.World journal of diabetes · 2025Article
- Epigenetic Modifications in the Retinal Pigment Epithelium of the Eye During RPE-Related Regeneration or Retinal Diseases in Vertebrates.Biomedicines · 2025Review
- DNA hypermethylation of PLTP mediated by DNMT3B aggravates vascular dysfunction in diabetic retinopathy via the AKT/GSK3β signaling pathway.Clinical epigenetics · 2025Article
- Potential mechanisms of epigenetic regulation in diabetic retinopathy from the perspectives of multi-omics.Diabetology & metabolic syndrome · 2025Article
- DNA methylation of long noncoding RNA cytochrome B in diabetic retinopathy.Non-coding RNA research · 2025Article
- Mitochondrial Dysfunction in Diabetes: Shedding Light on a Widespread Oversight.Pathophysiology : the official journal of the International Society for Pathophysiology · 2025Review
- Airway MMP-12 and DNA methylation in COPD: an integrative approach.Respiratory research · 2025Article
- Mitochondrial dysfunction in diabetic ulcers: pathophysiological mechanisms and targeted therapeutic strategies.Frontiers in cell and developmental biology · 2025Review
- Targeting oxidative stress in diabetic retinopathy: mechanisms, pathology, and novel treatment approaches.Frontiers in immunology · 2025Review
- TET2-mediated ECM1 hypomethylation promotes the neovascularization in active proliferative diabetic retinopathy.Clinical epigenetics · 2024Article
- Genetic insights and emerging therapeutics in diabetic retinopathy: from molecular pathways to personalized medicine.Frontiers in genetics · 2024Review
- Traversing the epigenetic landscape: DNA methylation from retina to brain in development and disease.Frontiers in cellular neuroscience · 2024Review
- Bergenin alleviates Diabetic Retinopathy in STZ-induced rats.Applied biochemistry and biotechnology · 2023Article
- The role of TET2-mediated ROBO4 hypomethylation in the development of diabetic retinopathy.Journal of translational medicine · 2023Article
- Epigenetic modifications and metabolic memory in diabetic retinopathy: beyond the surface.Neural regeneration research · 2023Review
- Epigenetics of the Pathogenesis and Complications of Type 2 Diabetes Mellitus.TouchREVIEWS in endocrinology · 2023Review
- Cross Talks between Oxidative Stress, Inflammation and Epigenetics in Diabetic Retinopathy.Cells · 2023Review
10 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Diabetes elevates matrix metalloproteinase-9 (MMP-9) in the retina and its capillary cells, and activated MMP-9 damages mitochondria, accelerating retinal capillary cell apoptosis, a phenomenon which precedes the development of retinopathy. Diabetes also favors epigenetic modifications regulating the expression of many genes. DNA methylation is maintained by methylating-hydroxymethylating enzymes, and retinal DNA methyltransferase (Dnmt) is activated in diabetes. Our aim is to investigate the role of DNA methylation in MMP-9 regulation. The effect of high glucose on 5-methylcytosine (5mC) and 5-hydroxymethyl cytosine (5hmC), and binding of Dnmt1 and hydroxymethylating enzyme (Tet2) on MMP-9 promoter were quantified in retinal endothelial cells. Specific role of Tet2 in MMP-9 activation was validated using Tet2-siRNA. The results were confirmed in the retina from streptozotocin-induced diabetic mouse. Although glucose increased Dnmt1 binding at MMP-9 promoter, it decreased 5mC levels. At the same promoter site, Tet2 binding and 5hmC levels were elevated. Tet2-siRNA ameliorated increase in 5hmC and MMP-9 transcription, and protected mitochondrial damage. Diabetic mice also presented similar dynamic DNA methylation changes in the retinal MMP-9 promoter. Thus, in diabetes transcription of retinal MMP-9 is maintained, in part, by an active DNA methylation-hydroxymethylation process, and regulation of this machinery should help maintain mitochondrial homeostasis and inhibit the development/progression of diabetic retinopathy.
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