title: Anti-neuropilin-1 peptide inhibition of synoviocyte survival, angiogenesis, and experimental arthritis.
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 (125)I-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 (125)I-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Catholic University of Korea, Seoul, South Korea.
authors.forename: Jin-Sun
authors.initials: JS
authors.lastname: Kong
authors.forename: Seung-Ah
authors.initials: SA
authors.lastname: Yoo
authors.forename: Jung-Wook
authors.initials: JW
authors.lastname: Kim
authors.forename: Seung-Pil
authors.initials: SP
authors.lastname: Yang
authors.forename: Chi-Bom
authors.initials: CB
authors.lastname: Chae
authors.forename: Valeria
authors.initials: V
authors.lastname: Tarallo
authors.forename: Sandro
authors.initials: S
authors.lastname: De Falco
authors.forename: Sung-Ho
authors.initials: SH
authors.lastname: Ryu
authors.forename: Chul-Soo
authors.initials: CS
authors.lastname: Cho
authors.forename: Wan-Uk
authors.initials: WU
authors.lastname: Kim
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D018501:Antirheumatic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D039942:Neuropilin-1 / Q000276:immunology*; D013583:Synovial Membrane / Q000187:drug effects / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology / Q000494:pharmacology
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D007155:Immunologic Factors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D039942:Neuropilin-1