Long pentraxin 3/tumor necrosis factor-stimulated gene-6 interaction a biological rheostat for fibroblast growth factor 2-mediated angiogenesis

Daria Leali, Antonio Inforzato, Roberto Ronca, Roberta Bianchi, Mirella Belleri, Daniela Coltrini, Emanuela Di Salle, Marina Sironi, Giuseppe Danilo Norata, Barbara Bottazzi, Cecilia Garlanda, Anthony J. Day, Marco Presta

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)696-703
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume32
Issue number3
DOIs
Publication statusPublished - Mar 2012

Keywords

  • angiogenesis
  • endothelium
  • FGF2
  • pentraxin
  • TSG-6

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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