ArticleKidney & blood pressure research2018
Enhanced Renal Afferent Arteriolar Reactive Oxygen Species and Contractility to Endothelin-1 Are Associated with Canonical Wnt Signaling in Diabetic Mice.
Article in Kidney & blood pressure research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- Precision Medicine: Therapeutically Targeting Mitochondrial Alterations in Heart Failure.JACC. Basic to translational science · 2025Review
- Unveiling mechanisms underlying kidney function changes during sex hormone therapy.The Journal of clinical investigation · 2025Observational
- Renal microcirculation and mechanisms in diabetic kidney disease.Frontiers in endocrinology · 2025Review
- Oxidative Stress, Reductive Stress and Antioxidants in Vascular Pathogenesis and Aging.Antioxidants (Basel, Switzerland) · 2023Review
- Article
- Indoxyl sulfate enhances endothelin-1-induced contraction via impairment of NO/cGMP signaling in rat aorta.Pflugers Archiv : European journal of physiology · 2021Article
- Article
- microRNA-378a Regulates the Reactive Oxygen Species (ROS)/Phosphatidylinositol 3-Kinases (PI3K)/AKT Signaling Pathway in Human Lens Epithelial Cells and Cataract.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
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Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
BACKGROUND/
aimsCanonical Wnt signaling is involved in oxidative stress, vasculopathy and diabetes mellitus but its role in diabetic renal microvascular dysfunction is unclear. We tested the hypothesis that enhanced canonical Wnt signaling in renal afferent arterioles from diabetic mice increases reactive oxygen species (ROS) and contractions to endothelin-1 (ET-1).
methodsStreptozotocin-induced diabetes or control C57Bl/6 mice received vehicle or sulindac (40 mg·kg-1·day-1) to block Wnt signaling for 4 weeks. ET-1 contractions were measured by changes of afferent arteriolar diameter. Arteriolar H2O2, O2 -, protein expression and enzymatic activity were assessed using sensitive fluorescence probes, immunoblotting and colorimetric assay separately.
resultsCompared to control, diabetic mouse afferent arteriole had increased O2- (+ 84%) and H2O2 (+ 91%) and enhanced responses to ET-1 at 10-8 mol·l-1 (-72±4% of versus -43±4%, P< 0.05) accompanied by reduced protein expressions and activities for catalase and superoxide dismutase 2 (SOD2). Arteriolar O2 - was increased further by ET-1 and contractions to ET-1 reduced by PEG-SOD in both groups whereas H2O2 unchanged by ET-1 and contractions were reduced by PEG-catalase selectively in diabetic mice. The Wnt signaling protein β-catenin was upregulated (3.3-fold decrease in p-β-catenin/β-catenin) while the glycogen synthase kinase-3β (GSK-3β) was downregulated (2.6-fold increase in p-GSK-3β/ GSK-3β) in preglomerular vessels of diabetic mice. Sulindac normalized the Wnt signaling proteins, arteriolar O2 -, H2O2 and ET-1 contractions while doubling microvascular catalase and SOD2 expression in diabetic mice.
conclusionIncreased ROS, notably H2O2 contributes to enhanced afferent arteriolar responses to ET-1 in diabetes, which is closely associated with Wnt signaling. Antioxidant pharmacological strategies targeting Wnt signaling may improve vascular function in diabetic nephropathy.
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