ArticleLaboratory investigation; a journal of technical methods and pathology2016
Activation of endothelial NAD(P)H oxidase accelerates early glomerular injury in diabetic mice.
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 26 papers.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- Ectopic lipid deposition in kidney diseases: mechanisms in specific cell types and therapeutic strategies.Frontiers in endocrinology · 2026Review
- Temporal glomerular gene expression dynamics during disease progression in a mouse model of hypertension-accelerated diabetic kidney disease.Animal models and experimental medicine · 2025Article
- Gut microbiota-derived indole-3-propionic acid alleviates diabetic kidney disease through its mitochondrial protective effect via reducing ubiquitination mediated-degradation of SIRT1.Journal of advanced research · 2025Article
- Specificity of endothelial cells in endothelial dysfunction of diabetic kidney disease and their crosstalk with neighboring cells: an updated review.Frontiers in endocrinology · 2025Review
- Renal microcirculation and mechanisms in diabetic kidney disease.Frontiers in endocrinology · 2025Review
- ASK-1 activation exacerbates kidney dysfunction via increment of glomerular permeability and accelerates cellular aging in diabetic kidney disease model mice.Scientific reports · 2024Article
- Crosstalk among podocytes, glomerular endothelial cells and mesangial cells in diabetic kidney disease: an updated review.Cell communication and signaling : CCS · 2024Review
- Early diabetic kidney disease: Focus on the glycocalyx.World journal of diabetes · 2023Review
- Importance of wnt-catenin signaling in hypertensive kidney diseases.Hypertension research : official journal of the Japanese Society of Hypertension · 2021Article
- Article
- Serum Albumin in Health and Disease: Esterase, Antioxidant, Transporting and Signaling Properties.International journal of molecular sciences · 2021Review
- SH3BP2 Deficiency Ameliorates Murine Systemic Lupus Erythematosus.International journal of molecular sciences · 2021Article
- Effect of zinc deficiency on chronic kidney disease progression and effect modification by hypoalbuminemia.PloS one · 2021Article
- Integrative Role of Albumin: Evolutionary, Biochemical and Pathophysiological Aspects.Journal of evolutionary biochemistry and physiology · 2021Article
- Forsythoside A Alleviates High Glucose-Induced Oxidative Stress and Inflammation in Podocytes by Inactivating MAPK Signaling via MMP12 Inhibition.Diabetes, metabolic syndrome and obesity : targets and therapy · 2021Article
- Molecular Mechanisms in Early Diabetic Kidney Disease: Glomerular Endothelial Cell Dysfunction.International journal of molecular sciences · 2020Review
- Beneficial Effect of Chloroquine and Amodiaquine on Type 1 Diabetic Tubulopathy by Attenuating Mitochondrial Nox4 and Endoplasmic Reticulum Stress.Journal of Korean medical science · 2020Article
- Cellular and molecular mechanisms of xenobiotics-induced premature senescence.Toxicology research · 2020Review
- Glomerular Endothelial Cells as Instigators of Glomerular Sclerotic Diseases.Frontiers in pharmacology · 2020Review
- Roles of Endovascular Calyx Related Enzymes in Endothelial Dysfunction and Diabetic Vascular Complications.Frontiers in pharmacology · 2020Article
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
Increased generation of reactive oxygen species (ROS) is a common denominative pathogenic mechanism underlying vascular and renal complications in diabetes mellitus. Endothelial NAD(P)H oxidase is a major source of vascular ROS, and it has an important role in endothelial dysfunction. We hypothesized that activation of endothelial NAD(P)H oxidase initiates and worsens the progression of diabetic nephropathy, particularly in the development of albuminuria. We used transgenic mice with endothelial-targeted overexpression of the catalytic subunit of NAD(P)H oxidase, Nox2 (NOX2TG). NOX2TG mice were crossed with Akita insulin-dependent diabetic (Akita) mice that develop progressive hyperglycemia. We compared the progression of diabetic nephropathy in Akita versus NOX2TG-Akita mice. NOX2TG-Akita mice and Akita mice developed significant albuminuria above the baseline at 6 and 10 weeks of age, respectively. Compared with Akita mice, NOX2TG-Akita mice exhibited higher levels of NAD(P)H oxidase activity in glomeruli, developed glomerular endothelial perturbations, and attenuated expression of glomerular glycocalyx. Moreover, in contrast to Akita mice, the NOX2TG-Akita mice had numerous endothelial microparticles (blebs), as detected by scanning electron microscopy, and increased glomerular permeability. Furthermore, NOX2TG-Akita mice exhibited distinct phenotypic changes in glomerular mesangial cells expressing α-smooth muscle actin, and in podocytes expressing increased levels of desmin, whereas the glomeruli generated increased levels of ROS. In conclusion, activation of endothelial NAD(P)H oxidase in the presence of hyperglycemia initiated and exacerbated diabetic nephropathy characterized by the development of albuminuria. Moreover, ROS generated in the endothelium compounded glomerular dysfunctions by altering the phenotypes of mesangial cells and compromising the integrity of the podocytes.
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