ArticleMolecular vision2016
PKR promotes choroidal neovascularization via upregulating the PI3K/Akt signaling pathway in VEGF expression.
Article in Molecular vision, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Identifying Choroidal Neovascularization-Associated Genes with GenePlexus in a Protein-Protein Interaction Network.Life (Basel, Switzerland) · 2026Article
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- Proteomic Investigation of Neurotrophic trans-Banglene Reveals Potential Link to Iron Homeostasis.Molecular neurobiology · 2025Article
- Unravelling the role of protein kinase R (PKR) in neurodegenerative disease: a review.Molecular biology reports · 2025Review
- A simplified protocol to induce hypoxia in a standard incubator: A focus on retinal cells.Experimental eye research · 2023Article
- Review
- Proteotranscriptomic analyses reveal distinct interferon-beta signaling pathways and therapeutic targets in choroidal neovascularization.Frontiers in immunology · 2023Article
- Cinnamaldehyde Downregulation of Sept9 Inhibits Glioma Progression through Suppressing Hif-1Disease markers · 2022Article
- Long non-coding RNA histone deacetylase 4 antisense RNA 1 (HDAC4-AS1) inhibits HDAC4 expression in human ARPE-19 cells with hypoxic stress.Bioengineered · 2021Article
- Network analysis and the impact of Aflibercept on specific mediators of angiogenesis in HUVEC cells.Journal of cellular and molecular medicine · 2021Article
- Involvement of TRPM2 Channel on Hypoxia-Induced Oxidative Injury, Inflammation, and Cell Death in Retinal Pigment Epithelial Cells: Modulator Action of Selenium Nanoparticles.Biological trace element research · 2021Article
- Inhibitory effects of safranal on laser-induced choroidal neovascularization and human choroidal microvascular endothelial cells and related pathways analyzed with transcriptome sequencing.International journal of ophthalmology · 2021Article
- IGFBP‑rP1‑silencing promotes hypoxia‑induced angiogenic potential of choroidal endothelial cells via the RAF/MEK/ERK signaling pathway.Molecular medicine reports · 2020Article
- Expression of Pro-Angiogenic Markers Is Enhanced by Blue Light in Human RPE Cells.Antioxidants (Basel, Switzerland) · 2020Article
- VEGF Production Is Regulated by the AKT/ERK1/2 Signaling Pathway and Controls the Proliferation ofFrontiers in cellular and infection microbiology · 2020Article
- Multiomics analyses of vesicular transport pathway-specific transcripts and proteins in ovine amnion: responses to altered intramembranous transport.Physiological genomics · 2019Article
- Optimization of an in vitro bilayer model for studying the functional interplay between human primary retinal pigment epithelial and choroidal endothelial cells isolated from donor eyes.BMC research notes · 2019Article
- PKR: A Kinase to Remember.Frontiers in molecular neuroscience · 2018Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe aim of this study was to investigate the functions of dsRNA-activated protein kinase (PKR) in choroidal neovascularization (CNV) and related signaling pathways in the production of vascular endothelial growth factor (VEGF).
methodsA chemical hypoxia model of in vitro RF/6A cells, a rhesus choroid-retinal endothelial cell line, was established by adding cobalt chloride (CoCl
resultsThe in vitro RF/6A cell chemical hypoxia model showed that PKR expression was upregulated in parallel with p-PI3K, p-Akt, and VEGF expression, peaking at 12 h. PKR siRNA downregulated PKR, p-PI3K, p-Akt, and VEGF expression. In addition, the PI3K inhibitor LY294002 greatly decreased the p-PI3K, p-Akt, and VEGF protein levels, but PKR expression was unaffected, indicating that Akt was a downstream molecule of PKR that upregulated VEGF expression. In the ARPE-19 (RPE cell line) and RF/6A cell coculture system, PKR siRNA reduced the migration and tube formation of the RF/6A cells. In vivo, PKR, p-PI3K, p-Akt, and VEGF expression increased and peaked at 7 days in the mouse CNV model induced by laser photocoagulation. Furthermore, on the RPE and choroid cryosections, PKR colocalized with CD31, suggesting that PKR was expressed by the vascular endothelium. The intravitreal injection of an anti-PKR monoclonal antibody decreased the progression and leakage area of CNV in mice.
conclusionsPKR promotes CNV formation via the PI3K/Akt signaling pathway in VEGF expression. Additionally, the anti-PKR monoclonal antibody significantly decreased CNV in a mouse model, showing the antibody may have therapeutic potential in human CNV.
Indexed as
Identifiers
27994435PMC5135740W2578315387What OpenQuestion holds
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.