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• W2191630306 abstract "Abstract Vascular endothelial growth factor (VEGF)-A-driven angiogenesis contributes to various disorders including cancer and proliferative diabetic retinopathy (PDR). Among several VEGF-A blockers clinically used is aflibercept, a chimeric VEGFR1/VEGFR2-based decoy receptor fused to the Fc fragment of IgG1 ( i.e. , VEGFR1/VEGFR2-Fc). Here, we revealed a novel anti-angiogenic function for aflibercept beyond its antagonism against VEGF family members. Immunoprecipitation and mass spectrometry analyses identified galectin-1 as an aflibercept-interacting protein. Biolayer interferometry revealed aflibercept binding to galectin-1 with higher affinity than VEGFR1-Fc and VEGFR2-Fc, which was abolished by deglycosylation of aflibercept with peptide: N -glycosidase F. Retinal LGALS1/Galectin-1 mRNA expression was enhanced in vitro by hypoxic stimulation and in vivo by induction of diseases including diabetes. Galectin-1 immunoreactivity co-localized with VEGFR2 in neovascular tissues surgically excised from human eyes with PDR. Compared with non-diabetic controls, intravitreal galectin-1 protein levels were elevated in PDR eyes, showing no correlation with increased VEGF-A levels. Preoperative injection of bevacizumab, a monoclonal antibody to VEGF-A, reduced the VEGF-A, but not galectin-1, levels. Galectin-1 application to human retinal microvascular endothelial cells up-regulated VEGFR2 phosphorylation, which was eliminated by aflibercept. Our present findings demonstrated the neutralizing efficacy of aflibercept against galectin-1, an angiogenic factor associated with PDR independently of VEGF-A." @default.
• W2191630306 created "2016-06-24" @default.
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• W2191630306 date "2015-12-09" @default.
• W2191630306 modified "2023-10-06" @default.
• W2191630306 title "Aflibercept Traps Galectin-1, an Angiogenic Factor Associated with Diabetic Retinopathy" @default.
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• W2191630306 doi "https://doi.org/10.1038/srep17946" @default.
• W2191630306 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4673700" @default.
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• W2191630306 hasPublicationYear "2015" @default.
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