ArticleThe Journal of biological chemistry2009
Pigment epithelium-derived factor maintains retinal pigment epithelium function by inhibiting vascular endothelial growth factor-R2 signaling through gamma-secretase.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
43 citing papers in PubMed, 67 citations in OpenAlex.
- Functional Roles of Pigment Epithelium-Derived Factor in Retinal Degenerative and Vascular Disorders: A Scoping Review.Investigative ophthalmology & visual science · 2024Article
- Small Extracellular Vesicle-Associated MiRNAs in Polarized Retinal Pigmented Epithelium.Investigative ophthalmology & visual science · 2024Article
- Retinal Vein Occlusion-Background Knowledge and Foreground Knowledge Prospects-A Review.Journal of clinical medicine · 2024Review
- Polarized Desmosome and Hemidesmosome Shedding via Small Extracellular Vesicles is an Early Indicator of Outer Blood-Retina Barrier Dysfunction.Journal of extracellular biology · 2023Article
- Notch Signaling in Acute Inflammation and Sepsis.International journal of molecular sciences · 2023Review
- Ethanol-Induced Oxidative Stress Modifies Inflammation and Angiogenesis Biomarkers in Retinal Pigment Epithelial Cells (ARPE-19): Role of CYP2E1 and its Inhibition by Antioxidants.Antioxidants (Basel, Switzerland) · 2020Article
- Pigment Epithelium-Derived Factor as a Possible Treatment Agent for Choroidal Neovascularization.Oxidative medicine and cellular longevity · 2020Review
- Review
- Autophagy: a new mechanism for regulating VEGF and PEDF expression in retinal pigment epithelium cells.International journal of ophthalmology · 2019Article
- Zika virus induces strong inflammatory responses and impairs homeostasis and function of the human retinal pigment epithelium.EBioMedicine · 2019Article
- A high content, small molecule screen identifies candidate molecular pathways that regulate rod photoreceptor outer segment renewal.Scientific reports · 2018Article
- VEGF-A selectively inhibits FLT1 ectodomain shedding independent of receptor activation and receptor endocytosis.American journal of physiology. Cell physiology · 2018Article
- Scleroderma fibroblasts suppress angiogenesis via TGF-β/caveolin-1 dependent secretion of pigment epithelium-derived factor.Annals of the rheumatic diseases · 2018Article
- A dock derived compound against laminin receptor (37 LR) exhibits anti-cancer properties in a prostate cancer cell line model.Oncotarget · 2018Article
- Genome-wide screen of gamma-secretase-mediated intramembrane cleavage of receptor tyrosine kinases.Molecular biology of the cell · 2017Article
- Directional Exosome Proteomes Reflect Polarity-Specific Functions in Retinal Pigmented Epithelium Monolayers.Scientific reports · 2017Article
- Progressive Early Breakdown of Retinal Pigment Epithelium Function in Hyperglycemic Rats.Investigative ophthalmology & visual science · 2016Article
- The small tellurium-based compound SAS suppresses inflammation in human retinal pigment epithelium.Molecular vision · 2016Article
- Pigment epithelium-derived factor: clinical significance in estrogen-dependent tissues and its potential in cancer therapy.Iranian journal of basic medical sciences · 2015Review
- Recombinant pigment epithelium-derived factor PEDF binds vascular endothelial growth factor receptors 1 and 2.In vitro cellular & developmental biology. Animal · 2015Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Wet age-related macular degeneration (AMD) attacks the integrity of the retinal pigment epithelium (RPE) barrier system. The pathogenic process was hypothesized to be mediated by vascular endothelial growth factor (VEGF) and antagonized by pigment epithelium-derived factor (PEDF). To dissect these functional interactions, monolayer cultures of RPE cells were established, and changes in transepithelial resistance were evaluated after administration of PEDF, placenta growth factor (VEGF-R1 agonist), and VEGF-E (VEGF-R2 agonist). A recently described mechanism of VEGF inhibition in endothelia required the release of VEGF-R1 intracellular domain by gamma-secretase. To evaluate this pathway in the RPE, cells were pretreated with inhibitors DAPT or LY411575. Processing of VEGF receptors was assessed by Western blot analysis. Administration of VEGF-E rapidly increased RPE permeability, and PEDF inhibited the VEGF-E response dose-dependently. Both gamma-secretase antagonists prevented the inhibitory effects of PEDF. The co-administration of PEDF and VEGF-E depleted the amount of VEGF-R2 in the membrane and increased the amount of VEGF-R2 ectodomain in the media. Therefore, the inhibitory effect of PEDF appears to be mediated via the processing of VEGF-R2 by gamma-secretase. gamma-Secretase generates the amyloid-beta (Abeta) peptide of Alzheimer disease from its precursor (amyloid precursor protein). This peptide is also a component of drusen in dry AMD. The results support the hypothesis that misregulation of gamma-secretase may not only lead to Abeta deposits in dry AMD but can also be damaging to RPE function by blocking the protective effects of PEDF to prevent VEGF from driving the dry to wet AMD transition.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.