We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Loss of SPARC-mediated VEGFR-1 suppression after injury reveals a novel antiangiogenic activity of VEGF-A.
- Authors
Nozaki, Miho; Sakurai, Eiji; Raisler, Brian J.; Baffi, Judit Z.; Witta, Jassir; Ogura, Yuichiro; Brekken, Rolf A.; Sage, E. Helene; Ambati, Balamurali K.; Ambati, Jayakrishna
- Abstract
VEGF-A promotes angiogenesis in many tissues. Here we report that choroidal neovascularization (CNV) incited by injury was increased by excess VEGF-A before injury but was suppressed by VEGF-A after injury. This unorthodox antiangiogenic effect was mediated via VEGFR-1 activation and VEGFR-2 deactivation, the latter via Src homology domain 2-containing (SH2-containing) tyrosine phosphatase-1 (SHP-1). The VEGFR-1-specific ligand placental growth factor-1 (PlGF-1), but not VEGF-E, which selectively binds VEGFR-2, mimicked these responses. Excess VEGF-A increased CNV before injury because VEGFR-1 activation was silenced by secreted protein, acidic and rich in cysteine (SPARC). The transient decline of SPARC after injury revealed a temporal window in which VEGF-A signaling was routed principally through VEGFR-1. These observations indicate that therapeutic design of VEGF-A inhibition should include consideration of the level and activity of SPARC.
- Subjects
VASCULAR endothelial growth factors; NEOVASCULARIZATION; PROTEIN-tyrosine phosphatase; CYTOKINES; GROWTH factors; CYTOLOGY; EYE anatomy; ANIMAL experimentation; CELL receptors; CELLULAR signal transduction; COMPARATIVE studies; ESTERASES; EYE; GLYCOPROTEINS; RESEARCH methodology; MEDICAL cooperation; MICE; NEOVASCULARIZATION inhibitors; PREGNANCY proteins; RESEARCH; EVALUATION research; SIGNAL peptides; PATHOLOGIC neovascularization
- Publication
Journal of Clinical Investigation, 2006, Vol 116, Issue 2, p422
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI26316