ArticleDiabetes2013
Regulation of matrix metalloproteinase-9 by epigenetic modifications and the development of diabetic retinopathy.
Article in Diabetes, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 136 citations in OpenAlex.
- Bone morphogenetic protein signaling as a key regulator of retinal fibrosis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Key role of transcription factors network in proliferative vitreoretinal diseases development.Cell & bioscience · 2026Review
- Beyond hyperglycemia: histone modification-mediated epigenetic dysregulation in diabetic retinopathy and nephropathy.Diabetology & metabolic syndrome · 2026Review
- Targeting the sirtuin 6-NF-κB p65 axis by 6-hydroxyhyoscyamine hydrobromide: a deacetylation-driven new therapy for diabetic wounds.Cellular & molecular biology letters · 2026Article
- Modulation of Oxidative Stress in Diabetic Retinopathy: Therapeutic Role of Natural Polyphenols.Antioxidants (Basel, Switzerland) · 2025Review
- Review
- Targeting oxidative stress in diabetic retinopathy: mechanisms, pathology, and novel treatment approaches.Frontiers in immunology · 2025Review
- Analysis of the Relationship Between Parkinson's Disease and Diabetic Retinopathy Based on Bioinformatics Methods.Molecular neurobiology · 2024Article
- Metabolic memory: mechanisms and diseases.Signal transduction and targeted therapy · 2024Review
- Effects of mesenchymal stromal cells and human recombinant Nerve Growth Factor delivered by bioengineered human corneal lenticule on an innovative model of diabetic retinopathy.Frontiers in endocrinology · 2024Article
- Epigenetic modifications and metabolic memory in diabetic retinopathy: beyond the surface.Neural regeneration research · 2023Review
- Review
- Cross Talks between Oxidative Stress, Inflammation and Epigenetics in Diabetic Retinopathy.Cells · 2023Review
- Advanced glycation end products regulate the receptor of AGEs epigenetically.Frontiers in cell and developmental biology · 2023Article
- Research Progress on Mitochondrial Dysfunction in Diabetic Retinopathy.Antioxidants (Basel, Switzerland) · 2022Review
- Diabetic Retinopathy: Are lncRNAs New Molecular Players and Targets?Antioxidants (Basel, Switzerland) · 2022Review
- On the Relationship between Diabetes and Obstructive Sleep Apnea: Evolution and Epigenetics.Biomedicines · 2022Review
- DNMT1-Mediated DNA Methylation Targets CDKN2B to Promote the Repair of Retinal Ganglion Cells in Streptozotocin-Induced Mongolian Gerbils during Diabetic Retinopathy.Computational and mathematical methods in medicine · 2022Article
- Long Noncoding RNAs and Mitochondrial Homeostasis in the Development of Diabetic Retinopathy.Frontiers in endocrinology · 2022Review
- Epigenetic modifications in diabetes.Metabolism: clinical and experimental · 2022Review
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Diabetes activates retinal matrix metalloproteinase-9 (MMP-9), and MMP-9 damages the mitochondria and augments capillary cell apoptosis. Our aim is to elucidate the mechanism responsible for MMP-9 activation. Histone modifications and recruitment of the nuclear transcriptional factor-κB (p65 subunit) at the MMP-9 promoter and the activity of lysine-specific demethylase 1 (LSD1) were measured in the retina from streptozotocin-induced diabetic rats. The role of LSD1 in MMP-9 activation was investigated in isolated retinal endothelial cells transfected with LSD1 small interfering RNA (siRNA). The results were confirmed in the retina from human donors with diabetic retinopathy. Diabetes decreased histone H3 dimethyl lysine 9 (H3K9me2) and increased acetyl H3K9 (Ac-H3K9) and p65 at the retinal MMP-9 promoter. LSD1 enzyme activity and its transcripts were elevated. LSD1 siRNA ameliorated the glucose-induced decrease in H3K9me2 and increase in p65 at the MMP-9 promoter, and prevented MMP-9 activation, mitochondrial damage, and cell apoptosis. Human donors with diabetic retinopathy had similar epigenetic changes at the MMP-9 promoter. Thus, activated LSD1 hypomethylates H3K9 at the MMP-9 promoter and this frees up that lysine 9 for acetylation. Increased Ac-H3K9 facilitates the recruitment of p65, resulting in MMP-9 activation and mitochondrial damage. Thus, the regulation of LSD1 by molecular or pharmacological means has the potential to retard the development of diabetic retinopathy.
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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.