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Quantitative Proteomics Reveals beta 2 Integrin-mediated Cytoskeletal Rearrangement in Vascular Endothelial Growth Factor (VEGF)-induced Retinal Vascular Hyperpermeability

Title
Quantitative Proteomics Reveals beta 2 Integrin-mediated Cytoskeletal Rearrangement in Vascular Endothelial Growth Factor (VEGF)-induced Retinal Vascular Hyperpermeability
Authors
Jo, DH[Jo, Dong Hyun]Bae, J[Bae, Jingi]Chae, S[Chae, Sehyun]Kim, JH[Kim, Jin Hyoung]Han, JH[Han, Jong-Hee]Hwang, D[Hwang, Daehee]Lee, SW[Lee, Sang-Won]Kim, JH[Kim, Jeong Hun]
DGIST Authors
Chae, S[Chae, Sehyun]; Hwang, D[Hwang, Daehee]
Issue Date
2016-05
Citation
Molecular and Cellular Proteomics, 15(5), 1681-1691
Type
Article
Article Type
Article
Keywords
Animal CellAnimal ExperimentAnimal ModelAnimal TissueCD18 AntigenControlled StudyCytoskeletal RearrangementCytoskeletonEndothelium CellIn Vitro StudyIn Vivo StudyMaleMouseNon-HumanPriority JournalProtein ExpressionProteomeProteomicsQuantitative AnalysisRetina DiseaseRetinal Vascular HyperpermeabilityVascular DiseaseVasculotropinVasculotropin Antibody
ISSN
1535-9476
Abstract
Retinal vascular hyperpermeability causes macular edema, leading to visual deterioration in retinal diseases such as diabetic retinopathy and retinal vascular occlusion. Dysregulation of junction integrity between endothelial cells by vascular endothelial growth factor (VEGF) was shown to cause retinal vascular hyperpermeability. Accordingly, anti-VEGF agents have been used to treat retinal vascular hyperpermeability. However, they can confer potential toxicity through their deleterious effects on maintenance and survival of neuronal and endothelial cells in the retina. Thus, it is important to identify novel therapeutic targets for retinal vascular hyperpermeability other than VEGF. Here, we prepared murine retinas showing VEGF-induced vascular leakage from superficial retinal vascular plexus and prevention of VEGF-induced leakage by anti-VEGF antibody treatment. We then performed comprehensive proteome profiling of these samples and identified retinal proteins for which abundances were differentially expressed by VEGF, but such alterations were inhibited by anti-VEGF antibody. Functional enrichment and network analyses of these proteins revealed the β2 integrin pathway, which can prevent dysregulation of junction integrity between endothelial cells through cytoskeletal rearrangement, as a potential therapeutic target for retinal vascular hyperpermeability. Finally, we experimentally demonstrated that inhibition of the β2 integrin pathway salvaged VEGF-induced retinal vascular hyperpermeability, supporting its validity as an alternative therapeutic target to anti-VEGF agents. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
URI
http://hdl.handle.net/20.500.11750/2691
DOI
10.1074/mcp.M115.053249
Publisher
American Society for Biochemistry and Molecular Biology Inc.
Related Researcher
  • Author Hwang, Dae Hee Systems Biology and Medicine Lab
  • Research Interests Multilayered spatiotemporal networks; Regulatory motifs or pathways; Metabolite-protein networks; Network stochasticity; Proteomics and informatics
Files:
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Collection:
New BiologyETC1. Journal Articles


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