Anti-Neuropilin-1 Peptide Inhibition of Synoviocyte Survival, Angiogenesis, and Experimental Arthritis
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SCOPUS
- Title
- Anti-Neuropilin-1 Peptide Inhibition of Synoviocyte Survival, Angiogenesis, and Experimental Arthritis
- Authors
- Kong, JS; Yoo, SA; Kim, JW; Yang, SP; Chae, CB; Tarallo, V; De Falco, S; Ryu, SH; Cho, CS; Kim, WU
- Date Issued
- 2010-01
- Publisher
- willy interscience
- Abstract
- Objective. To delineate the role of neuropilin-1 (NP-1), a vascular endothelial growth factor receptor (VEGFR), in rheumatoid inflammation and to determine whether blockade of NP-1 could suppress synoviocyte survival and angiogenesis. Methods. VEGF(111-165) peptide, which encompasses the NP-1 binding domain of VEGF(165), was generated by cleaving VEGF(165) with plasmin. The effect of this peptide on the interaction between VEGF(165) and its receptor was determined by I-125-VEGFR binding assay. Assays to determine synoviocyte apoptosis, adhesion, and migration were performed in the presence of VEGF(165) and/ or the peptide. VEGF(165)-induced angiogenesis was assessed by measuring the proliferation, tube formation, and wounding migration of endothelial cells (ECs). Mice were immunized with type II collagen to induce experimental arthritis. Results. VEGF(111-165) peptide specifically inhibited the binding of I-125-VEGF(165) to NP-1 on rheumatoid synoviocytes and ECs. The peptide eliminated the VEGF(165)-mediated increase in synoviocyte survival and activation of p-ERK and Bcl-2. The peptide also completely inhibited a VEGF(165)-induced increase in synoviocyte adhesion and migration. In addition, the anti-NP-1 peptide blocked VEGF(165)-stimulated proliferation, capillary tube formation, and wounding migration of ECs in vitro. VEGF(165)-induced neovascularization in a Matrigel plug in mice was also blocked by treatment with the peptide. Finally, subcutaneous injection of anti-NP-1 peptide suppressed arthritis severity and autoantibody formation in mice with experimental arthritis and inhibited synoviocyte hyperplasia and angiogenesis in arthritic joints. Conclusion. Anti-NP-1 peptide suppressed VEGF(165)-induced increases in synoviocyte survival and angiogenesis, and thereby blocked experimental arthritis. Our findings suggest that anti-NP-1 peptide could be useful in alleviating chronic arthritis.
- Keywords
- ENDOTHELIAL GROWTH-FACTOR; ELEMENT-BINDING PROTEIN; RHEUMATOID-ARTHRITIS; IN-VIVO; SOLUBLE NEUROPILIN-1; FACTOR DETERMINANTS; BCL-2 EXPRESSION; CELL-MIGRATION; FACTOR VEGF; RECEPTOR
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/26306
- DOI
- 10.1002/art.27243
- ISSN
- 0004-3591
- Article Type
- Article
- Citation
- ARTHRITIS AND RHEUMATISM, vol. 62, no. 1, page. 179 - 190, 2010-01
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