Interaction of Vascular Endothelial Growth Factor 165 with Neuropilin-1 Protects Rheumatoid Synoviocytes from Apoptotic Death by Regulating Bcl-2 Expression and Bax Translocation

摘要: Rheumatoid arthritis (RA) synoviocytes are resistant to apoptosis and exhibit a transformed phenotype, which might be caused by chronic exposure genotoxic stimuli including reactive oxygen species growth factors. In this study, we investigated the role of vascular endothelial factor165 (VEGF165), potent angiogenic factor, its receptor in synoviocytes. We demonstrated here that neuropilin-1, rather than fms-like tyrosine kinase-1 kinase insert domain-containing receptor, is major VEGF165 fibroblast-like Neuropilin-1 was highly expressed lining layer, infiltrating leukocytes, cells rheumatoid synovium. The production VEGF165, ligand for neuropilin, significantly higher RA osteoarthritis ligation recombinant prevented induced serum starvation or sodium nitroprusside (SNP). rapidly triggered phospho-Akt phospho-ERK activity then Bcl-2 expression Akt ERK inhibitor cancelled protective effect on SNP-induced synoviocyte apoptosis. Moreover, blocks down-regulation as well Bax translocation from cytosol mitochondria. neuropilin-1 transcripts short interfering RNA spontaneous apoptosis, associated with both decrease increase Collectively, our data suggest interaction crucial survival provide important implications abnormal therapeutic intervention RA.