ArticleDiabetes2023
Sustained Upregulation of Endothelial Nox4 Mediates Retinal Vascular Pathology in Type 1 Diabetes.
Article in Diabetes, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Integrative gene target mapping, RNA sequencing, in silico molecular docking, ADMET profiling and molecular dynamics simulation study of marine derived molecules for type 1 diabetes mellitus.Molecular diversity · 2026Article
- Metabolic pathways and cell death modalities in diabetic complications: unraveling pyroptosis, ferroptosis, cuproptosis, and disulfidptosis.Cell death discovery · 2026Review
- HDAC3 mediates retinal endothelial cell metabolic reprogramming and angiogenesis.Acta pharmacologica Sinica · 2026Article
- Gingerenone A attenuates diabetic vascular remodeling through AMPK/mTOR/S6K1 signaling.Frontiers in pharmacology · 2026Article
- Nox3 expression and function in retinal ganglion cells and Amacrine cells.Cellular and molecular life sciences : CMLS · 2025Article
- Role of Matricellular Proteins in Endothelial Cell Inflammation and Atherosclerosis.Antioxidants (Basel, Switzerland) · 2025Review
- Redox Regulation of Microvascular Physiology and Pathophysiology: Insights into Therapeutic Strategies and Limitations.Antioxidants & redox signaling · 2025Review
- Restoration of NOX4 signalling reverses endothelial colony-forming cell angiogenic dysfunction associated with experimental and clinical diabetes.Stem cell research & therapy · 2025Article
- LDL-c/HDL-c Ratio and NADPH-Oxidase-2-Derived Oxidative Stress as Main Determinants of Microvascular Endothelial Function in Morbidly Obese Subjects.Antioxidants (Basel, Switzerland) · 2024Article
- Intragland Expression of the Shh Gene Alleviates Irradiation-Induced Salivary Gland Injury through Microvessel Protection and the Regulation of Oxidative Stress.Antioxidants (Basel, Switzerland) · 2024Article
- NADPH oxidase 4-derived hydrogen peroxide counterbalances testosterone-induced endothelial dysfunction and migration.American journal of physiology. Endocrinology and metabolism · 2024Article
- Two ferroptosis-specific expressed genes NOX4 and PARP14 are considered as potential biomarkers for the diagnosis and treatment of diabetic retinopathy and atherosclerosis.Diabetology & metabolic syndrome · 2024Article
- Role of MicroRNA in linking diabetic retinal neurodegeneration and vascular degeneration.Frontiers in endocrinology · 2024Review
- Effects of Nox4 upregulation on PECAM-1 expression in a mouse model of diabetic retinopathy.PloS one · 2024Article
- The Slow Progression of Diabetic Retinopathy Is Associated with Transient Protection of Retinal Vessels from Death.International journal of molecular sciences · 2023Article
- Maternal exercise represses Nox4 via SIRT1 to prevent vascular oxidative stress and endothelial dysfunction in SHR offspring.Frontiers in endocrinology · 2023Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
NADPH oxidase 4 (Nox4) is a major source of reactive oxygen species (ROS) in retinal endothelial cells (ECs) and is upregulated under hyperglycemic and hypoxic conditions. However, the role of endothelial Nox4 upregulation in long-term retinal blood vessel damage in diabetic retinopathy (DR) remains undefined. Here, we attempted to address this question using humanized EC-specific Nox4 transgenic (hNox4EC-Tg) and EC-specific Nox4 knockout (Nox4EC-KO) mouse models. Our results show that hNox4EC-Tg mice at age of 10-12 months exhibited increased tortuosity of retinal blood vessels, focal vascular leakage, and acellular capillary formation. In vitro study revealed enhanced apoptosis in brain microvascular ECs derived from hNox4EC-Tg mice, concomitant with increased mitochondrial ROS, elevated lipid peroxidation, decreased mitochondrial membrane potential, and reduced mitochondrial respiratory function. In contrast, EC-specific deletion of Nox4 decreased mitochondrial ROS generation, alleviated mitochondrial damage, reduced EC apoptosis, and protected the retina from acellular capillary formation and vascular hyperpermeability in a streptozotocin-induced diabetes mouse model. These findings suggest that sustained upregulation of Nox4 in the endothelium contributes to retinal vascular pathology in diabetes, at least in part, through impairing mitochondrial function. Normalization of Nox4 expression in ECs may provide a new approach for prevention of vascular injury in DR.
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Registered trials
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