Long pentraxin 3/tumor necrosis factor-stimulated gene-6 interaction a biological rheostat for fibroblast growth factor 2-mediated angiogenesis
|dc.contributor.author||Di Salle, E.|
|dc.identifier.citation||Leali, D. and Inforzato, A. and Ronca, R. and Bianchi, R. and Belleri, M. and Coltrini, D. and Di Salle, E. et al. 2012. Long pentraxin 3/tumor necrosis factor-stimulated gene-6 interaction a biological rheostat for fibroblast growth factor 2-mediated angiogenesis. Arteriosclerosis, Thrombosis, and Vascular Biology. 32 (3): pp. 696-703.|
Objective-Angiogenesis is regulated by the balance between pro-and antiangiogenic factors and by extracellular matrix protein interactions. Fibroblast growth factor 2 (FGF2) is a major proangiogenic inducer inhibited by the interaction with the soluble pattern recognition receptor long pentraxin 3 (PTX3). PTX3 is locally coexpressed with its ligand tumor necrosis factor-stimulated gene-6 (TSG-6), a secreted glycoprotein that cooperates with PTX3 in extracellular matrix assembly. Here, we characterized the effect of TSG-6 on PTX3/FGF2 interaction and FGF2-mediated angiogenesis. Methods and Results-Solid phase binding and surface plasmon resonance assays show that TSG-6 and FGF2 bind the PTX3 N-terminal domain with similar affinity. Accordingly, TSG-6 prevents FGF2/PTX3 interaction and suppresses the inhibition exerted by PTX3 on heparan sulfate proteoglycan/FGF2/FGF receptor complex formation and on FGF2-dependent angiogenesis in vitro and in vivo. Also, endogenous PTX3 exerts an inhibitory effect on vascularization induced by FGF2 in a murine subcutaneous Matrigel plug assay, the inhibition being abolished in Ptx3-null mice or by TSG-6 treatment in wild-type animals. Conclusion-TSG-6 reverts the inhibitory effects exerted by PTX3 on FGF2-mediated angiogenesis through competition of FGF2/PTX3 interaction. This may provide a novel mechanism to control angiogenesis in those pathological settings characterized by the coexpression of TSG-6 and PTX3, in which the relative levels of these proteins may fine-tune the angiogenic activity of FGF2. © 2012 American Heart Association, Inc.
|dc.publisher||Lippincott Williams & Wilkins|
|dc.title||Long pentraxin 3/tumor necrosis factor-stimulated gene-6 interaction a biological rheostat for fibroblast growth factor 2-mediated angiogenesis|
|dcterms.source.title||Arteriosclerosis, Thrombosis, and Vascular Biology|
|curtin.department||School of Biomedical Sciences|
|curtin.accessStatus||Open access via publisher|
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