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

Dong Hyun Jo, Jingi Bae, Sehyun Chae, Jin Hyoung Kim, Jong Hee Han, Daehee Hwang, Sang Won Lee, Jeong Hun Kim

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1681-1691
Number of pages11
JournalMolecular and Cellular Proteomics
Volume15
Issue number5
DOIs
Publication statusPublished - 2016 May

Bibliographical note

Funding Information:
This work was supported the Bio-Signal Analysis Technology Innovation Program 2009-0090895, Pioneer Research Program 2012-0009544, the Bio and Medical Technology Development Program (2015M3A9E6028949, 2015M3A9E6028947) from NRF/MEST, Republic of Korea, Seoul National University Research Grant 800-20140542, Multi-omics Research Program NRF-2012M3A9B9036675, National Research Foundation Grant NRF-2014M3C7A1046047, and Institute for Basic Science Grant IBS-R013-G1-2015-a00 funded by the Korean Ministry of Science, ICT & Future Planning.

Publisher Copyright:
© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Molecular Biology

Fingerprint

Dive into the research topics of 'Quantitative proteomics reveals β2 integrin-mediated cytoskeletal rearrangement in vascular endothelial growth factor (VEGF)- induced retinal vascular hyperpermeability'. Together they form a unique fingerprint.

Cite this