ArticleInvestigative ophthalmology & visual science2014
Sirt1, a negative regulator of matrix metalloproteinase-9 in diabetic retinopathy.
Article in Investigative ophthalmology & visual science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.
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75 citing papers in PubMed, 1 synthesis or guideline pooled it, 127 citations in OpenAlex.
- Effect of Resveratrol on In Vitro and In Vivo Models of Diabetic Retinophathy: A Systematic Review.International journal of molecular sciences · 2019Pooled it
- Diabetic retinopathy: shaped by the "hidden hand" of post-translational modifications.Molecular neurodegeneration · 2026Review
- Aging and cancer: current understandings and future perspectives.Signal transduction and targeted therapy · 2026Review
- Beyond hyperglycemia: histone modification-mediated epigenetic dysregulation in diabetic retinopathy and nephropathy.Diabetology & metabolic syndrome · 2026Review
- Article
- Vitreous MMP-2, TIMP-1, and TIMP-2 Levels in Vitreoretinal Pathologies: A Prospective Analysis of 181 Eyes.International journal of molecular sciences · 2025Article
- Modulation of Oxidative Stress in Diabetic Retinopathy: Therapeutic Role of Natural Polyphenols.Antioxidants (Basel, Switzerland) · 2025Review
- Applications of Matrix Metalloproteinase-9-Related Nanomedicines in Tumors and Vascular Diseases.Pharmaceutics · 2025Review
- A cross-sectional study on the comparison of serum SIRT-1 and MMP-9 levels of patients with bronchiectasis and healthy controls.Pakistan journal of medical sciences · 2025Article
- Beneficial effects of resveratrol on diabetes mellitus and its complications: focus on mechanisms of action.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Targeting oxidative stress in diabetic retinopathy: mechanisms, pathology, and novel treatment approaches.Frontiers in immunology · 2025Review
- In Diabetic Aged Female Rats, Resveratrol Supplementation Prevents Retinal Tissue Damage By Increasing Antioxidant Activity Through SIRT1 Gene Expression.Noro psikiyatri arsivi · 2025Article
- Mitochondrial DNA transcription and mitochondrial genome-encoded long noncoding RNA in diabetic retinopathy.Mitochondrion · 2024Article
- A comprehensive review on the neuroprotective potential of resveratrol in ischemic stroke.Heliyon · 2024Review
- Dysregulation of histone deacetylases in ocular diseases.Archives of pharmacal research · 2024Review
- Causal relationships between blood metabolites and diabetic retinopathy: a two-sample Mendelian randomization study.Frontiers in endocrinology · 2024Article
- Targeting the Epigenetic Marks in Type 2 Diabetes Mellitus: Will Epigenetic Therapy Be a Valuable Adjunct to Pharmacotherapy?Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Review
- Genetic modification of miR-34a enhances efficacy of transplanted human dental pulp stem cells after ischemic stroke.Neural regeneration research · 2023Article
- Epigenetic changes underlie the association between diabetes mellitus and oral diseases.Molecular biology reports · 2023Review
- Epigenetic modifications and metabolic memory in diabetic retinopathy: beyond the surface.Neural regeneration research · 2023Review
15 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
purposeIn the pathogenesis of diabetic retinopathy, matrix metalloproteinase (MMP)-9 damages retinal mitochondria, activating the apoptotic machinery. Transcription of MMP-9 is regulated by nuclear factor kappa B (NF-κB), and the activation of NF-κB is modulated by the acetylation of its p65 subunit. Sirtuin 1 (Sirt1), a deacetylase, plays an important role in the acetylation-deacetylation of p65. The goal of this study is to investigate the role of Sirt1 in the activation of MMP-9 in diabetic retinopathy.
methodsThe effect of hyperglycemia and Sirt1 activator, resveratrol, on acetylation of p65 and its binding at MMP-9 promoter-and mitochondrial damage and apoptosis-was assessed in the retinal endothelial cells. Role of oxidative stress in the regulation of Sirt1 was evaluated in the cells incubated in H2O2. The results were confirmed in the retina from diabetic mice with Sod2 or MMP-9 gene manipulated.
resultsHigh glucose decreased Sirt1 activity and increased p65 acetylation, and resveratrol prevented increase in p65 acetylation, binding of p65 at MMP-9 promoter and MMP-9 activation, mitochondria damage, and cell apoptosis. While Sirt1 was decreased by H2O2, MMP-9 was significantly increased. Retina from wild-type diabetic mice presented similar decrease in Sirt1, and diabetic mice with Sod2 overexpression or MMP-9 deletion had normal retinal Sirt1. Retinal microvasculature from human donors with established diabetic retinopathy also had decreased Sirt1.
conclusionsThus, in diabetes, increase in oxidative stress inhibits Sirt1 and p65 is hyperacetylated, increasing the binding of p65 at MMP-9 promoter. Prevention of Sirt1 inhibition, via modulating acetylation of p65, should protect activation of MMP-9 and inhibit the development of diabetic retinopathy.
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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.