ArticlePloS one2014
Vascular endothelial growth factor-receptor 1 inhibition aggravates diabetic nephropathy through eNOS signaling pathway in db/db mice.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Single-cell insights into maladaptive endothelial plasticity and therapeutic targets in diabetic vascular complications.Cardiovascular diabetology · 2026Review
- Logic-based modeling of inflammatory macrophage cross talk with glomerular endothelial cells in diabetic kidney disease.American journal of physiology. Renal physiology · 2025Article
- Impact of Nintedanib and Anti-Angiogenic Agents on Uveal Melanoma Cell Behavior.Investigative ophthalmology & visual science · 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
- Dissecting VEGF-induced acute versus chronic vascular hyperpermeability: Essential roles of dimethylarginine dimethylaminohydrolase-1.iScience · 2021Article
- Role of VEGF-A and LRG1 in Abnormal Angiogenesis Associated With Diabetic Nephropathy.Frontiers in physiology · 2020Review
- Fucoxanthin Alleviates Oxidative Stress through Akt/Sirt1/FoxO3α Signaling to Inhibit HG-Induced Renal Fibrosis in GMCs.Marine drugs · 2019Article
- Astragaloside IV protects against diabetic nephropathy via activating eNOS in streptozotocin diabetes-induced rats.BMC complementary and alternative medicine · 2019Article
- Renal reabsorption in 3D vascularized proximal tubule models.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Low dose radiation primed iNOS + M1macrophages modulate angiogenic programming of tumor derived endothelium.Molecular carcinogenesis · 2018Article
- Tc-99m and Fluorescence-Labeled Anti-Flt1 Peptide as a Multimodal Tumor Imaging Agent Targeting Vascular Endothelial Growth Factor-Receptor 1.Nuclear medicine and molecular imaging · 2018Article
- Human chorionic villous mesenchymal stem/stromal cells protect endothelial cells from injury induced by high level of glucose.Stem cell research & therapy · 2018Article
- VEGF165b Modulates Endothelial VEGFR1-STAT3 Signaling Pathway and Angiogenesis in Human and Experimental Peripheral Arterial Disease.Circulation research · 2017Article
- Antiangiogenic Therapy for Diabetic Nephropathy.BioMed research international · 2017Review
- PlGF/VEGFR-1 Signaling Promotes Macrophage Polarization and Accelerated Tumor Progression in Obesity.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Article
- Influence of the Expression of Inflammatory Markers on Kidney after Fetal Programming in an Experimental Model of Renal Failure.Journal of immunology research · 2016Article
- Multiphasic changes in systemic VEGF following intravitreal injections of ranibizumab in a child.Eye (London, England) · 2015Article
- Canonical and noncanonical vascular endothelial growth factor pathways: new developments in biology and signal transduction.Arteriosclerosis, thrombosis, and vascular biology · 2015Review
- Involvement of inflammation-related miR-155 and miR-146a in diabetic nephropathy: implications for glomerular endothelial injury.BMC nephrology · 2014Article
- Liraglutide Exerts Antidiabetic Effect via PTP1B and PI3K/Akt2 Signaling Pathway in Skeletal Muscle of KKAy Mice.International journal of endocrinology · 2014Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The manipulation of vascular endothelial growth factor (VEGF)-receptors (VEGFRs) in diabetic nephropathy is as controversial as issue as ever. It is known to be VEGF-A and VEGFR2 that regulate most of the cellular actions of VEGF in experimental diabetic nephropathy. On the other hand, such factors as VEGF-A, -B and placenta growth factor bind to VEGFR1 with high affinity. Such notion instigated us to investigate on whether selective VEGFR1 inhibition with GNQWFI hexamer aggravates the progression of diabetic nephropathy in db/db mice. While diabetes suppressed VEGFR1, it did increase VEGFR2 expressions in the glomerulus. Db/db mice with VEGFR1 inhibition showed more prominent features with respect to, albuminuria, mesangial matrix expansion, inflammatory cell infiltration and greater numbers of apoptotic cells in the glomerulus, and oxidative stress than that of control db/db mice. All these changes were related to the suppression of diabetes-induced increases in PI3K activity and Akt phosphorylation as well as the aggravation of endothelial dysfunction associated with the inactivation of FoxO3a and eNOS-NOx. In cultured human glomerular endothelial cells (HGECs), high-glucose media with VEGFR1 inhibition induced more apoptotic cells and oxidative stress than did high-glucose media alone, which were associated with the suppression of PI3K-Akt phosphorylation, independently of the activation of AMP-activated protein kinase, and inactivation of FoxO3a and eNOS-NOx pathway. In addition, transfection with VEGFR1 siRNA in HGECs also suppressed PI3K-Akt-eNOS signaling. In conclusion, the specific blockade of VEGFR1 with GNQWFI caused severe renal injury related to profound suppression of the PI3K-Akt, FoxO3a and eNOS-NOx pathway, giving rise to the oxidative stress-induced apoptosis of glomerular cells in type 2 diabetic nephropathy.
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