| First Author | Simantov R | Year | 2005 |
| Journal | Matrix Biol | Volume | 24 |
| Issue | 1 | Pages | 27-34 |
| PubMed ID | 15748999 | Mgi Jnum | J:96478 |
| Mgi Id | MGI:3530701 | Doi | 10.1016/j.matbio.2004.11.005 |
| Citation | Simantov R, et al. (2005) The antiangiogenic effect of thrombospondin-2 is mediated by CD36 and modulated by histidine-rich glycoprotein. Matrix Biol 24(1):27-34 |
| abstractText | Thrombospondins-1 and -2 (TSP-1, TSP-2) are matricellular glycoproteins with potent antiangiogenic activity. We have previously shown that the antiangiogenic activity of TSP-1 is mediated by the interaction of the type I repeats (TSR) with the receptor CD36, although other domains of TSP-1 have also been implicated. We now show that the antiangiogenic activity of TSP-2, which contains three TSRs but, unlike TSP-1, lacks the capacity to activate TGF-beta, is similarly dependent on CD36. Using the corneal pocket assay we found that TSP-2 did not inhibit bFGF-induced angiogenesis in CD36 null mice. We then demonstrated that (125)[I]-TSP-2 bound to murine macrophages and that binding was diminished by 70% by anti-CD36 antibody or by using cells from CD36 null animals. Solid-phase binding studies revealed that (125)[I]-TSP-2 bound to CD36/glutathione-S-transferase (GST) fusion proteins encoding the region spanning amino acids 93-120, but not amino acids 298-439. This 93-120 amino acid region, previously identified as the TSP-1 binding site, is homologous to domains on other TSP binding proteins, such as LIMP-2 and histidine-rich glycoprotein (HRGP). Finally, we showed with an immunoabsorbent binding assay that TSP-2 bound HRGP with high affinity and that HRGP blocked the antiangiogenic activity of TSP-2, acting like a 'decoy' receptor. These data suggest that modulation of the TSR/CD36 system may play an important role in the regulation of the angiogenic 'switch,' and may provide a target for therapeutic interventions. |
