ArticleInternational journal of molecular sciences2020
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.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 55 citations in OpenAlex.
- Effects of New P2X7R Antagonists on Retinal Inflammatory Degenerative Conditions.Inflammation · 2026Article
- AAV2.7m8-Mediated MicroRNA Expression Suppresses VEGF-Induced Angiogenic Responses in HUVEC.International journal of molecular sciences · 2026Article
- Oligosaccharides Reduce the Survival ofInsects · 2026Article
- SGLT2 inhibitors and diabetic retinopathy progression: evidence from a retrospective cohort study and Mendelian randomization analysis.Frontiers in endocrinology · 2026Article
- Identification of angiogenesis-related hub genes in proliferative diabetic retinopathy via integrated transcriptomics and machine learning.Diabetology & metabolic syndrome · 2025Article
- Ginkgo Biloba extract attenuates diabetic retinopathy progression by modulating TP53 ubiquitination in a rat model.Molecular biology reports · 2025Article
- Endothelial MEMO1 Regulates Angiogenic Signaling in a Model of Retinopathy of Prematurity.FASEB bioAdvances · 2025Article
- Elucidating programmed cell death in diabetic retinal microangionopathy and neurodegeneration: unraveling molecular mechanisms and therapeutic actions of natural products.Inflammopharmacology · 2025Review
- YTHDF3-mediated FLCN/cPLA2 axis improves cardiac fibrosis via suppressing lysosomal function.Acta pharmacologica Sinica · 2025Article
- Diabetic Retinopathy-A Review.Current diabetes reviews · 2025Review
- GPR120/FFAR4 protects retinal vascular endothelial cells against high glucose injuryInternational journal of ophthalmology · 2025Article
- Article
- Solid Lipid Nanoparticles Encapsulating a Benzoxanthene Derivative in a Model of the Human Blood-Brain Barrier: Modulation of Angiogenic Parameters and Inflammation in Vascular Endothelial Growth Factor-Stimulated Angiogenesis.Molecules (Basel, Switzerland) · 2024Article
- Molecular Mechanisms and Therapeutic Implications of Human Pericyte-like Adipose-Derived Mesenchymal Stem Cells in an In Vitro Model of Diabetic Retinopathy.International journal of molecular sciences · 2024Article
- Fenofibrate and diabetic retinopathy.Medical hypothesis, discovery & innovation ophthalmology journal · 2024Review
- Vascular Endothelial Growth Factor A (VEGFA) Regulates Hepatic Lipid and Glycogen Metabolism inInternational journal of molecular sciences · 2023Article
- Prolonged Exposure to High Glucose Induces Premature Senescence Through Oxidative Stress and Autophagy in Retinal Pigment Epithelial Cells.Archivum immunologiae et therapiae experimentalis · 2023Article
- Protective Effects of Human Pericyte-like Adipose-Derived Mesenchymal Stem Cells on Human Retinal Endothelial Cells in an In Vitro Model of Diabetic Retinopathy: Evidence for Autologous Cell Therapy.International journal of molecular sciences · 2023Article
- Pericytes of Stria Vascularis Are Targets of Cisplatin-Induced Ototoxicity: New Insights into the Molecular Mechanisms Involved in Blood-Labyrinth Barrier Breakdown.International journal of molecular sciences · 2022Article
- Differences in Multifocal Electroretinogram Study in Two Populations of Type 1 and Type 2 Diabetes Mellitus Patients without Diabetic Retinopathy.Journal of clinical medicine · 2022Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Early blood retinal barrier (BRB) dysfunction induced by hyperglycemia was related to increased pro-inflammatory activity of phospholipase A2 (PLA2) and the upregulation of vascular endothelial growth factor A (VEGF-A). Here, we tested the role of VEGF-A in high glucose (HG)-induced damage of human retinal endothelial cells (HRECs) mediated by Ca++-dependent (cPLA2) and Ca++-independent (iPLA2) PLA2s. HRECs were treated with normal glucose (5 mM, NG) or high glucose (25 mM, HG) for 48 h with or without the VEGF-trap Aflibercept (Afl, 40 µg/mL), the cPLA2 inhibitor arachidonoyl trifluoromethyl ketone (AACOCF3; 15 µM), the iPLA2 inhibitor bromoenol lactone (BEL; 5 µM), or VEGF-A (80 ng/mL). Both Afl and AACOCF3 prevented HG-induced damage (MTT and LDH release), impairment of angiogenic potential (tube-formation), and expression of VEGF-A mRNA. Furthermore, Afl counteracted HG-induced increase of phospho-ERK and phospho-cPLA2 (immunoblot). VEGF-A in HG-medium increased glucose toxicity, through upregulation of phospho-ERK, phospho-cPLA2, and iPLA2 (about 55%, 45%, and 50%, respectively); immunocytochemistry confirmed the activation of these proteins. cPLA2 knockdown by siRNA entirely prevented cell damage induced by HG or by HG plus VEGF-A, while iPLA2 knockdown produced a milder protective effect. These data indicate that VEGF-A mediates the early glucose-induced damage in retinal endothelium through the involvement of ERK1/2/PLA2 axis activation.
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Registered trials
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