ArticleBlood2013
Both Kdr and Flt1 play a vital role in hypoxia-induced Src-PLD1-PKCγ-cPLA(2) activation and retinal neovascularization.
Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
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- A Disintegrin and Metalloproteinase 10 Regulates Ephrin B2-Mediated Endothelial Cell Sprouting and Ischemic Retinopathy.The American journal of pathology · 2025Article
- Vascular endothelial growth factor signaling in health and disease: from molecular mechanisms to therapeutic perspectives.Signal transduction and targeted therapy · 2025Review
- Hypoxia-Induced Inflammation in In Vitro Model of Human Blood-Brain Barrier: Modulatory Effects of the Olfactory Ensheathing Cell-Conditioned Medium.Molecular neurobiology · 2025Article
- Comparison of HIF-1α and survivin levels in patients with diabetes and retinopathy of varying severity.Arquivos brasileiros de oftalmologia · 2024Article
- A cell transcriptomic profile provides insights into adipocytes of porcine mammary gland across development.Journal of animal science and biotechnology · 2023Article
- Vascular cell-adhesion molecule 1 (VCAM-1) regulates JunB-mediated IL-8/CXCL1 expression and pathological neovascularization.Communications biology · 2023Article
- IL-33 enhances Jagged1 mediated NOTCH1 intracellular domain (NICD) deubiquitination and pathological angiogenesis in proliferative retinopathy.Communications biology · 2022Article
- Upregulated phospholipase D2 expression and activity is related to the metastatic properties of melanoma.Oncology letters · 2022Article
- Novel Role of Prereplication Complex Component Cell Division Cycle 6 in Retinal Neovascularization.Arteriosclerosis, thrombosis, and vascular biology · 2022Article
- A Genome-Wide Analysis of the Gene Expression and Alternative Splicing Events in a Whole-Body Hypoxic Preconditioning Mouse Model.Neurochemical research · 2021Article
- Activation of the VEGF-A/ERK/PLA2 Axis Mediates Early Retinal Endothelial Cell Damage Induced by High Glucose: New Insight from an In Vitro Model of Diabetic Retinopathy.International journal of molecular sciences · 2020Article
- PKCθ-JunB axis via upregulation of VEGFR3 expression mediates hypoxia-induced pathological retinal neovascularization.Cell death & disease · 2020Article
- Systematic large-scale meta-analysis identifies miRNA-429/200a/b and miRNA-141/200c clusters as biomarkers for necrotizing enterocolitis in newborn.Bioscience reports · 2019Article
- Counteracting the effect of leukemia exosomes by antiangiogenic gold nanoparticles.International journal of nanomedicine · 2019Article
- A new role for cofilin in retinal neovascularization.Journal of cell science · 2016Article
- Predicted molecular signaling guiding photoreceptor cell migration following transplantation into damaged retina.Scientific reports · 2016Article
- Cyclic AMP Response Element Binding Protein Mediates Pathological Retinal Neovascularization via Modulating DLL4-NOTCH1 Signaling.EBioMedicine · 2015Article
- Binding of VEGF-A is sufficient to abrogate the disturbing effects of VEGF-B together with VEGF-A on retinal endothelial cells.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2015Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
To understand the mechanisms of Src-PLD1-PKCγ-cPLA2 activation by vascular endothelial growth factor A (VEGFA), we studied the role of Kdr and Flt1. VEGFA, while having no effect on Flt1 phosphorylation, induced Kdr phosphorylation in human retinal microvascular endothelial cells (HRMVECs). Depletion of Kdr attenuated VEGFA-induced Src-PLD1-PKCγ-cPLA2 activation. Regardless of its phosphorylation state, downregulation of Flt1 also inhibited VEGFA-induced Src-PLD1-PKCγ-cPLA2 activation, but only modestly. In line with these findings, depletion of either Kdr or Flt1 suppressed VEGFA-induced DNA synthesis, migration, and tube formation, albeit more robustly with Kdr downregulation. Hypoxia induced tyrosine phosphorylation of Kdr and Flt1 in mouse retina, and depletion of Kdr or Flt1 blocked hypoxia-induced Src-PLD1-PKCγ-cPLA2 activation and retinal neovascularization. VEGFB induced Flt1 tyrosine phosphorylation and Src-PLD1-PKCγ-cPLA2 activation in HRMVECs. Hypoxia induced VEGFA and VEGFB expression in retina, and inhibition of their expression blocked hypoxia-induced Kdr and Flt1 activation, respectively. Furthermore, depletion of VEGFA or VEGFB attenuated hypoxia-induced Src-PLD1-PKCγ-cPLA2 activation and retinal neovascularization. These findings suggest that although VEGFA, through Kdr and Flt1, appears to be the major modulator of Src-PLD1-PKCγ-cPLA2 signaling in HRMVECs, facilitating their angiogenic events in vitro, both VEGFA and VEGFB mediate hypoxia-induced Src-PLD1-PKCγ-cPLA2 activation and retinal neovascularization via activation of Kdr and Flt1, respectively.
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Registered trials
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