ArticleScientific reports2021
Regulation of Rac1 transcription by histone and DNA methylation in diabetic retinopathy.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- Beyond hyperglycemia: histone modification-mediated epigenetic dysregulation in diabetic retinopathy and nephropathy.Diabetology & metabolic syndrome · 2026Review
- Protein prenylation in islet β-cell function in health and metabolic stress.Biochemical pharmacology · 2025Review
- Review
- Identifying therapeutic target genes for diabetic retinopathy using systematic druggable genome-wide Mendelian randomization.Diabetology & metabolic syndrome · 2025Article
- Review
- Advances in molecular epidemiology of diabetic retinopathy: from genomics to gut microbiomics.Molecular biology reports · 2025Review
- Targeting oxidative stress in diabetic retinopathy: mechanisms, pathology, and novel treatment approaches.Frontiers in immunology · 2025Review
- Antibody-based therapeutics and therapeutic development for diabetic retinopathy: targeting VEGF, Ang/Tie, and inflammatory pathways.Frontiers in endocrinology · 2025Review
- The role of RAC1 in resistance to targeted therapies in cancer.Small GTPases · 2024Review
- Gestational Hypoxia Impaired Endothelial Nitric Oxide Synthesis Via miR-155-5p/NADPH Oxidase/Reactive Oxygen Species Axis in Male Offspring Vessels.Journal of the American Heart Association · 2024Article
- SIRT1/P53 in retinal pigment epithelial cells in diabetic retinopathy: a gene co-expression analysis and He-Ying-Qing-Re formula treatment.Frontiers in molecular biosciences · 2024Article
- Regulatory roles of CARD9-BCL10-Rac1 (CBR) signalome in islet β-cell function in health and metabolic stress: Is there room for MALT1?Biochemical pharmacology · 2023Review
- Epigenetic modifications and metabolic memory in diabetic retinopathy: beyond the surface.Neural regeneration research · 2023Review
- Single Nucleotide Polymorphisms of theBiomedicines · 2023Article
- Regulation of serine palmitoyl-transferase and Rac1-Nox2 signaling in diabetic retinopathy.Scientific reports · 2022Article
- Evaluation of Radial Peripapillary Capillary Density in G6PD Deficiency: An OCT Angiography Pilot Study.Journal of clinical medicine · 2022Article
- The pathophysiological mechanisms underlying diabetic retinopathy.Frontiers in cell and developmental biology · 2022Review
- Epigenetic modifications in diabetes.Metabolism: clinical and experimental · 2022Review
- Diabetic Retinopathy and NADPH Oxidase-2: A Sweet Slippery Road.Antioxidants (Basel, Switzerland) · 2021Review
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Cytosolic ROS, generated by NADPH oxidase 2 (Nox2) in diabetes, damage retinal mitochondria, which leads to the development of retinopathy. A small molecular weight G-protein essential for Nox2 activation, Rac1, is also transcriptionally activated via active DNA methylation-hydroxymethylation. DNA methylation is a dynamic process, and can also be regulated by histone modifications; diabetes alters retinal histone methylation machinery. Our aim is to investigate the role of histone methylation (H3K9me3) of Rac1 promoter in dynamic DNA methylation- transcriptional activation. Using human retinal endothelial cells in 20 mM D-glucose, H3K9me3 at Rac1 promoter was quantified by chromatin-Immunoprecipitation technique. Crosstalk between H3K9me3 and DNA methylation was examined in cells transfected with siRNA of histone trimethyl-transferase, Suv39H1, or Dnmt1, exposed to high glucose. Key parameters were confirmed in retinal microvessels from streptozotocin-induced diabetic mice, with intravitreally administered Suv39H1-siRNA or Dnmt1-siRNA. Compared to cells in normal glucose, high glucose increased H3K9me3 and Suv39H1 binding at Rac1 promoter, and Suv39H1-siRNA prevented glucose-induced increase 5 hydroxy methyl cytosine (5hmC) and Rac1 mRNA. Similarly, in diabetic mice, Suv39H1-siRNA attenuated increase in 5hmC and Rac1 mRNA. Thus, H3K9me3 at Rac1 promoter assists in active DNA methylation-hydroxymethylation, activating Rac1 transcription. Regulation of Suv39H1-H3K9 trimethylation could prevent further epigenetic modifications, and prevent diabetic retinopathy.
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