title: Long pentraxin 3/tumor necrosis factor-stimulated gene-6 interaction: a biological rheostat for fibroblast growth factor 2-mediated angiogenesis.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biomedical Sciences and Biotechnology, School of Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
authors.forename: Daria
authors.initials: D
authors.lastname: Leali
authors.forename: Antonio
authors.initials: A
authors.lastname: Inforzato
authors.forename: Roberto
authors.initials: R
authors.lastname: Ronca
authors.forename: Roberta
authors.initials: R
authors.lastname: Bianchi
authors.forename: Mirella
authors.initials: M
authors.lastname: Belleri
authors.forename: Daniela
authors.initials: D
authors.lastname: Coltrini
authors.forename: Emanuela
authors.initials: E
authors.lastname: Di Salle
authors.forename: Marina
authors.initials: M
authors.lastname: Sironi
authors.forename: Giuseppe Danilo
authors.initials: GD
authors.lastname: Norata
authors.forename: Barbara
authors.initials: B
authors.lastname: Bottazzi
authors.forename: Cecilia
authors.initials: C
authors.lastname: Garlanda
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Day
authors.forename: Marco
authors.initials: M
authors.lastname: Presta
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002097:C-Reactive Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016466:CHO Cells; D002417:Cattle; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002642:Chick Embryo; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D011994:Recombinant Proteins / Q000378:metabolism; D000683:Serum Amyloid P-Component / Q000235:genetics / Q000378:metabolism*; D020349:Surface Plasmon Resonance; D014162:Transfection; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D015815:Cell Adhesion Molecules; D016222:Fibroblast Growth Factor 2; D019812:Heparan Sulfate Proteoglycans; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D000683:Serum Amyloid P-Component; D000099153:Pentraxins; C072273:TNFAIP6 protein, human