ArticleThe Journal of biological chemistry2013
Pigment epithelium-derived factor (PEDF) prevents retinal cell death via PEDF Receptor (PEDF-R): identification of a functional ligand binding site.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Association of PEDF polymorphisms with age-related macular degeneration and polypoidal choroidal vasculopathy: a systematic review and meta-analysis.Scientific reports · 2015Pooled it
- Mechanistic insights into the role of PEDF-R (PNPLA2) in photoreceptors.Bioscience reports · 2026Review
- Complexity of PEDF multifunctional signaling in retinal development and diseases.Communications biology · 2026Article
- Pigment Epithelium-Derived Factor From Müller Cells Is Involved in Angiopoietin-Mediated Survival Control of Retinal Neurons.Investigative ophthalmology & visual science · 2026Article
- Gene-Agnostic Therapeutic Strategies for Inherited Retinal Diseases: Neuroprotection and Immunomodulation.Genes · 2026Review
- Outcomes of subretinal macular hemorrhage treatment: a 7-year retrospective cohort study at Oslo University Hospital.International journal of retina and vitreous · 2025Article
- Lack of Pnpla2 Accelerates Progression of AMD-Like Features in Mice.Investigative ophthalmology & visual science · 2025Article
- A role of pigment epithelium-derived factor in zinc-mediated mechanism of neurodegeneration in glaucoma.Communications biology · 2025Article
- H105A peptide eye drops promote photoreceptor survival in murine and human models of retinal degeneration.Communications medicine · 2025Article
- Deletion of Pnpla2 Causes Malformation and Malperformance of Mouse Photoreceptors.Advances in experimental medicine and biology · 2025Article
- Molecular insights into foveal hypoplasia: development, genetics, mechanisms, and models.Molecular vision · 2025Review
- Functional Roles of Pigment Epithelium-Derived Factor in Retinal Degenerative and Vascular Disorders: A Scoping Review.Investigative ophthalmology & visual science · 2024Article
- H105A peptide eye drops promote photoreceptor survival in murine and human models of retinal degeneration.bioRxiv : the preprint server for biology · 2024Article
- A new R,R-RvD6 isomer with protective actions following corneal nerve injury.Prostaglandins & other lipid mediators · 2024Review
- Molecular mechanisms underlying inherited photoreceptor degeneration as targets for therapeutic intervention.Frontiers in cellular neuroscience · 2024Review
- Ablation of pigment epithelium-derived factor receptor (PEDF-R/Pnpla2) causes photoreceptor degeneration.Journal of lipid research · 2023Article
- Potential application value of pigment epithelium-derived factor in sensorineural hearing loss.Frontiers in neuroscience · 2023Review
- PEDF Deletion Induces Senescence and Defects in Phagocytosis in the RPE.International journal of molecular sciences · 2022Article
- Expression and production of pigment epithelium-derived factor (PEDF) and PEDF receptor variants from mammalian and bacterial cells.Protein expression and purification · 2022Article
- Pigment Epithelium Derived Factor Is Involved in the Late Phase of Osteosarcoma Metastasis by Increasing Extravasation and Cell-Cell Adhesion.Frontiers in oncology · 2022Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The extracellular pigment epithelium-derived factor (PEDF) displays retina survival activity by interacting with receptor proteins on cell surfaces. We have previously reported that PEDF binds and stimulates PEDF receptor (PEDF-R), a transmembrane phospholipase. However, the PEDF binding site of PEDF-R and its involvement in survival activity have not been identified. The purpose of this work is to identify a biologically relevant ligand-binding site on PEDF-R. PEDF bound the PEDF-R ectodomain L4 (Leu(159)-Met(325)) with affinity similar to the full-length PEDF-R (Met(1)-Leu(504)). Binding assays using synthetic peptides spanning L4 showed that PEDF selectively bound E5b (Ile(193)-Leu(232)) and P1 (Thr(210)-Leu(249)) peptides. Recombinant C-terminal truncated PEDF-R4 (Met(1)-Leu(232)) and internally truncated PEDF-R and PEDF-R4 (ΔHis(203)-Leu(232)) retained phospholipase activity of the full-length PEDF-R. However, PEDF-R polypeptides without the His(203)-Leu(232) region lost the PEDF affinity that stimulated their enzymatic activity. Cell surface labeling showed that PEDF-R is present in the plasma membranes of retina cells. Using siRNA to selectively knock down PEDF-R in retina cells, we demonstrated that PEDF-R is essential for PEDF-mediated cell survival and antiapoptotic activities. Furthermore, preincubation of PEDF with P1 and E5b peptides blocked the PEDF·PEDF-R-mediated retina cell survival activity, implying that peptide binding to PEDF excluded ligand-receptor interactions on the cell surface. Our findings establish that PEDF-R is required for the survival and antiapoptotic effects of PEDF on retina cells and has determinants for PEDF binding within its L4 ectodomain that are critical for enzymatic stimulation.
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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.