ArticleJournal of clinical medicine2020
VEGFR2 Blockade Improves Renal Damage in an Experimental Model of Type 2 Diabetic Nephropathy.
Article in Journal of clinical medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 38 citations in OpenAlex.
- Mesangial Cells (MES-SV40) Cultured in High Glucose Produce IL-36α, Which Is Associated with Type 2 Diabetes Mellitus.International journal of molecular sciences · 2026Article
- Nutrient-Derived Modulation of the Gremlin-1/BMP-4 Axis by White Tea Preserves Insulin Sensitivity During Early Diet-Induced Metabolic Dysregulation.International journal of molecular sciences · 2026Article
- Unraveling the power of peptides fromNarra J · 2025Article
- Network pharmacology analysis and experimental validation elucidate the protective mechanisms of BYHWD against hypoxia/reoxygenation-induced endothelial cell injury.Frontiers in medicine · 2025Article
- Exploring the Molecular Modalities in the Pathogenesis of Diabetic Kidney Disease with a Focus on the Potential Therapeutic Implications.Biomedicines · 2024Review
- The KDR Gene rs2071559 and the VEGF Gene rs6921438 May Be Associated with Diabetic Nephropathy in Caucasians with Type 2 Diabetes Mellitus.International journal of molecular sciences · 2024Article
- Mitochondrial metabolic reprogramming in diabetic kidney disease.Cell death & disease · 2024Review
- The Expression and Molecular Mechanisms of Matrix Metalloproteinase- 9 and Vascular Endothelial Growth Factor in Renal Interstitial Fibrosis in Rats.Current molecular medicine · 2024Article
- Impact of baicalin and components of Scutellaria baicalensis on renal fibrosis of diabetic kidney disease.Frontiers in pharmacology · 2024Article
- Inhibition of Xanthine Oxidase Protects against Diabetic Kidney Disease through the Amelioration of Oxidative Stress via VEGF/VEGFR Axis and NOX-FoxO3a-eNOS Signaling Pathway.International journal of molecular sciences · 2023Article
- VEGFR2 insufficiency enhances phosphotoxicity and undermines Klotho's protection against peritubular capillary rarefaction and kidney fibrosis.American journal of physiology. Renal physiology · 2023Article
- Effect of subacute poisoning with lambdacyhalothrin on vascular endothelial growth factor 2 receptor in mice kidneys.BMC nephrology · 2022Article
- Meta-Inflammation and De Novo Lipogenesis Markers Are Involved in Metabolic Associated Fatty Liver Disease Progression in BTBR ob/ob Mice.International journal of molecular sciences · 2022Article
- Epigenetic Modulation of Gremlin-1/NOTCH Pathway in Experimental Crescentic Immune-Mediated Glomerulonephritis.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Kidney microRNA Expression Pattern in Type 2 Diabetic Nephropathy in BTBR Ob/Ob Mice.Frontiers in pharmacology · 2022Article
- Study of the Active Components and Molecular Mechanism ofFrontiers in molecular biosciences · 2021Article
- Article
- Pathogenic Pathways and Therapeutic Approaches Targeting Inflammation in Diabetic Nephropathy.International journal of molecular sciences · 2020Review
- Special Issue "Diabetic Nephropathy: Diagnosis, Prevention and Treatment".Journal of clinical medicine · 2020Article
- A Network Pharmacology-Based Strategy for Unveiling the Mechanisms of Tripterygium Wilfordii Hook F against Diabetic Kidney Disease.Journal of diabetes research · 2020Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The absence of optimal treatments for Diabetic Nephropathy (DN) highlights the importance of the search for novel therapeutic targets. The vascular endothelial growth factor receptor 2 (VEGFR2) pathway is activated in experimental and human DN, but the effects of its blockade in experimental models of DN is still controversial. Here, we test the effects of a therapeutic anti-VEGFR2 treatment, using a VEGFR2 kinase inhibitor, on the progression of renal damage in the BTBR ob/ob (leptin deficiency mutation) mice. This experimental diabetic model develops histological characteristics mimicking the key features of advanced human DN. A VEGFR2 pathway-activation blockade using the VEGFR2 kinase inhibitor SU5416, starting after kidney disease development, improves renal function, glomerular damage (mesangial matrix expansion and basement membrane thickening), tubulointerstitial inflammation and tubular atrophy, compared to untreated diabetic mice. The downstream mechanisms involved in these beneficial effects of VEGFR2 blockade include gene expression restoration of podocyte markers and downregulation of renal injury biomarkers and pro-inflammatory mediators. Several ligands can activate VEGFR2, including the canonical ligands VEGFs and GREMLIN. Activation of a GREMLIN/VEGFR2 pathway, but not other ligands, is correlated with renal damage progression in BTBR ob/ob diabetic mice. RNA sequencing analysis of GREMLIN-regulated genes confirm the modulation of proinflammatory genes and related-molecular pathways. Overall, these data show that a GREMLIN/VEGFR2 pathway activation is involved in diabetic kidney disease and could potentially be a novel therapeutic target in this clinical condition.
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