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Quantitative Proteomics Reveals beta 2 Integrin-mediated Cytoskeletal Rearrangement in Vascular Endothelial Growth Factor (VEGF)-induced Retinal Vascular Hyperpermeability
- Quantitative Proteomics Reveals beta 2 Integrin-mediated Cytoskeletal Rearrangement in Vascular Endothelial Growth Factor (VEGF)-induced Retinal Vascular Hyperpermeability
- 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
- Molecular and Cellular Proteomics, 15(5), 1681-1691
- Article Type
- Animal Cell; Animal Experiment; Animal Model; Animal Tissue; CD18 Antigen; Controlled Study; Cytoskeletal Rearrangement; Cytoskeleton; Endothelium Cell; In Vitro Study; In Vivo Study; Male; Mouse; Non-Human; Priority Journal; Protein Expression; Proteome; Proteomics; Quantitative Analysis; Retina Disease; Retinal Vascular Hyperpermeability; Vascular Disease; Vasculotropin; Vasculotropin Antibody
- 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.
- American Society for Biochemistry and Molecular Biology Inc.
- Related Researcher
Hwang, Dae Hee
Systems Biology and Medicine Lab
Multilayered spatiotemporal networks; Regulatory motifs or pathways; Metabolite-protein networks; Network stochasticity; Proteomics and informatics
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