Long pentraxin 3/tumor necrosis factor-stimulated gene-6 interaction a biological rheostat for fibroblast growth factor 2-mediated angiogenesis
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 (...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal Article |
| Published: |
Lippincott Williams & Wilkins
2012
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| Online Access: | http://hdl.handle.net/20.500.11937/55514 |
| _version_ | 1848759641200132096 |
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| author | Leali, D. Inforzato, A. Ronca, R. Bianchi, R. Belleri, M. Coltrini, D. Di Salle, E. Sironi, M. Norata, Giuseppe Bottazzi, B. Garlanda, C. Day, A. Presta, M. |
| author_facet | Leali, D. Inforzato, A. Ronca, R. Bianchi, R. Belleri, M. Coltrini, D. Di Salle, E. Sironi, M. Norata, Giuseppe Bottazzi, B. Garlanda, C. Day, A. Presta, M. |
| author_sort | Leali, D. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T10:03:06Z |
| format | Journal Article |
| id | curtin-20.500.11937-55514 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T10:03:06Z |
| publishDate | 2012 |
| publisher | Lippincott Williams & Wilkins |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-555142017-09-13T16:11:11Z Long pentraxin 3/tumor necrosis factor-stimulated gene-6 interaction a biological rheostat for fibroblast growth factor 2-mediated angiogenesis Leali, D. Inforzato, A. Ronca, R. Bianchi, R. Belleri, M. Coltrini, D. Di Salle, E. Sironi, M. Norata, Giuseppe Bottazzi, B. Garlanda, C. Day, A. Presta, M. 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. 2012 Journal Article http://hdl.handle.net/20.500.11937/55514 10.1161/ATVBAHA.111.243998 Lippincott Williams & Wilkins unknown |
| spellingShingle | Leali, D. Inforzato, A. Ronca, R. Bianchi, R. Belleri, M. Coltrini, D. Di Salle, E. Sironi, M. Norata, Giuseppe Bottazzi, B. Garlanda, C. Day, A. Presta, M. Long pentraxin 3/tumor necrosis factor-stimulated gene-6 interaction a biological rheostat for fibroblast growth factor 2-mediated angiogenesis |
| title | Long pentraxin 3/tumor necrosis factor-stimulated gene-6 interaction a biological rheostat for fibroblast growth factor 2-mediated angiogenesis |
| title_full | Long pentraxin 3/tumor necrosis factor-stimulated gene-6 interaction a biological rheostat for fibroblast growth factor 2-mediated angiogenesis |
| title_fullStr | Long pentraxin 3/tumor necrosis factor-stimulated gene-6 interaction a biological rheostat for fibroblast growth factor 2-mediated angiogenesis |
| title_full_unstemmed | Long pentraxin 3/tumor necrosis factor-stimulated gene-6 interaction a biological rheostat for fibroblast growth factor 2-mediated angiogenesis |
| title_short | Long pentraxin 3/tumor necrosis factor-stimulated gene-6 interaction a biological rheostat for fibroblast growth factor 2-mediated angiogenesis |
| title_sort | long pentraxin 3/tumor necrosis factor-stimulated gene-6 interaction a biological rheostat for fibroblast growth factor 2-mediated angiogenesis |
| url | http://hdl.handle.net/20.500.11937/55514 |