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식물노화·수명연구단
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Quantitative proteomics reveals β2 integrin-mediated cytoskeletal rearrangement in vascular endothelial growth factor (VEGF)- induced retinal vascular hyperpermeability

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Title
Quantitative proteomics reveals β2 integrin-mediated cytoskeletal rearrangement in vascular endothelial growth factor (VEGF)- induced retinal vascular hyperpermeability
Author(s)
Jo D.H.; Bae J.; Sehyun Chae; Kim J.H.; Han J.-H.; Daehee Hwang; Lee S.-W.; Kim J.H.
Publication Date
2016-05
Journal
MOLECULAR & CELLULAR PROTEOMICS, v.15, no.5, pp.1681 - 1691
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
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
https://pr.ibs.re.kr/handle/8788114/2516
DOI
10.1074/mcp.M115.053249
ISSN
1535-9476
Appears in Collections:
Center for Plant Aging Research (식물 노화·수명 연구단) > 1. Journal Papers (저널논문)
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