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http://purl.uniprot.org/citations/35970387http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/35970387http://www.w3.org/2000/01/rdf-schema#comment"Placental growth factor (PlGF) belongs to the vascular endothelial growth factor (VEGF) family of proteins that participate in angiogenesis and vasculogenesis. Anti-VEGF therapy has become the standard treatment for ocular angiogenic disorders in ophthalmological practice. However, there is emerging evidence that anti-VEGF treatment may increase the risk of atrophy of the retinal pigment epithelium (RPE), which is important for the homeostasis of retinal tissue. Whereas the cytoprotective role of VEGF family molecules, particularly that of VEGF A (VEGFA) through its receptor VEGF receptor-2 (VEGFR-2), has been recognized, the physiological role of PlGF in the retina is still unknown. In this study, we explored the role of PlGF in the RPE using PlGF-knockdown RPE cells generated by retrovirus-based PlGF-shRNA transduction. We show that VEGFA reduced apoptosis induced by serum starvation in RPE cells, whereas the antiapoptotic effect of VEGFA was abrogated by VEGFR-2 knockdown. Furthermore, PlGF knockdown increased serum starvation-induced cell apoptosis and unexpectedly reduced the protein level of VEGFR-2 in the RPE. The antiapoptotic effect of VEGFA was also diminished in PlGF-knockdown RPE cells. In addition, we found that glycogen synthase kinase 3 activity was involved in proteasomal degradation of VEGFR-2 in RPE cells and inactivated by PlGF via AKT phosphorylation. Overall, the present data demonstrate that PlGF is crucial for RPE cell viability and that PlGF supports VEGFA/VEGFR-2 signaling by stabilizing the VEGFR-2 protein levels through glycogen synthase kinase 3 inactivation."xsd:string
http://purl.uniprot.org/citations/35970387http://purl.org/dc/terms/identifier"doi:10.1016/j.jbc.2022.102378"xsd:string
http://purl.uniprot.org/citations/35970387http://purl.uniprot.org/core/author"Ishida S."xsd:string
http://purl.uniprot.org/citations/35970387http://purl.uniprot.org/core/author"Wu D."xsd:string
http://purl.uniprot.org/citations/35970387http://purl.uniprot.org/core/author"Murata M."xsd:string
http://purl.uniprot.org/citations/35970387http://purl.uniprot.org/core/author"Noda K."xsd:string
http://purl.uniprot.org/citations/35970387http://purl.uniprot.org/core/author"Hase K."xsd:string
http://purl.uniprot.org/citations/35970387http://purl.uniprot.org/core/author"Ando R."xsd:string
http://purl.uniprot.org/citations/35970387http://purl.uniprot.org/core/author"Kase S."xsd:string
http://purl.uniprot.org/citations/35970387http://purl.uniprot.org/core/date"2022"xsd:gYear
http://purl.uniprot.org/citations/35970387http://purl.uniprot.org/core/name"J Biol Chem"xsd:string
http://purl.uniprot.org/citations/35970387http://purl.uniprot.org/core/pages"102378"xsd:string
http://purl.uniprot.org/citations/35970387http://purl.uniprot.org/core/title"Placental growth factor stabilizes VEGF receptor-2 protein in retinal pigment epithelial cells by downregulating glycogen synthase kinase 3 activity."xsd:string
http://purl.uniprot.org/citations/35970387http://purl.uniprot.org/core/volume"298"xsd:string
http://purl.uniprot.org/citations/35970387http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/35970387
http://purl.uniprot.org/citations/35970387http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/35970387
http://purl.uniprot.org/uniprot/#_A0A0U2WZU8-mappedCitation-35970387http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/35970387
http://purl.uniprot.org/uniprot/#_A0A0U2X4C8-mappedCitation-35970387http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/35970387
http://purl.uniprot.org/uniprot/#_A0A0H4A777-mappedCitation-35970387http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/35970387
http://purl.uniprot.org/uniprot/#_A0A0H4A7S0-mappedCitation-35970387http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/35970387
http://purl.uniprot.org/uniprot/#_A0A0H4A7S4-mappedCitation-35970387http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/35970387
http://purl.uniprot.org/uniprot/#_A0A0H4ADZ1-mappedCitation-35970387http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/35970387
http://purl.uniprot.org/uniprot/#_A0A0H4AF76-mappedCitation-35970387http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/35970387
http://purl.uniprot.org/uniprot/#_A0A0H4AF85-mappedCitation-35970387http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/35970387