The hypothesis that thrombospondin-1 (TSP-1) can exert opposite effects on angiogenesis depending on the functional status of its domains/fragments was investigated. In the rabbit cornea, TSP-1 inhibited angiogenesis induced by fibroblast growth factor-2 (FGF-2). However, when tested per se, TSP-1 was able to elicit an angiogenic response comparable to that induced by FGF-2. Induction of angiogenesis was dose-dependent (20 ng - 2 μg/pellet), was prevented by anti-TSP antibodies or by heat-inactivation of TSP-1, and was not due to inflammatory mediators, to FGF-2 or to TGF-β. Equimolar concentrations of the 25 kDa heparin binding fragment of TSP-1 were even more efficient than the whole molecule, and promoted the angiogenic activity of FGF-2. On the contrary, the 140 kDa fragment of TSP-1 did not induce angiogenesis and turned off the angiogenic response to FGF-2. The 25 kDa fragment and TSP-1, but not the 140 kDa fragment, increased endothelial cell invasiveness and stimulated the production and activation of matrix metalloproteinase-2 (MMP-2). Moreover, the 25 kDa fragment reduced the synthesis of the MMP-2 inhibitor TIMP-2, while the 140 kDa fragment caused a twofold increase in TIMP-2 production and inhibited MMPs stimulation by TSP-1 and FGF-2. We conclude that TSP-1 is a source of smaller mediators of angiogenesis, which affect in an opposite way endothelial cell functions and proteolytic activity, thus resulting in an opposite final effect on angiogenesis.

G., T., Morbidelli, L., Donnini, S., A., P., H. J., G., R., G., et al. (2000). The heparin binding 25kDa fragment of thrombospondin-1 promotes angiogenesis and modulates gelatinases and TIMP-2 in endothelial cells. THE FASEB JOURNAL, 14(12), 1674-1676.

The heparin binding 25kDa fragment of thrombospondin-1 promotes angiogenesis and modulates gelatinases and TIMP-2 in endothelial cells

MORBIDELLI, LUCIA;DONNINI, SANDRA;ZICHE, MARINA
2000-01-01

Abstract

The hypothesis that thrombospondin-1 (TSP-1) can exert opposite effects on angiogenesis depending on the functional status of its domains/fragments was investigated. In the rabbit cornea, TSP-1 inhibited angiogenesis induced by fibroblast growth factor-2 (FGF-2). However, when tested per se, TSP-1 was able to elicit an angiogenic response comparable to that induced by FGF-2. Induction of angiogenesis was dose-dependent (20 ng - 2 μg/pellet), was prevented by anti-TSP antibodies or by heat-inactivation of TSP-1, and was not due to inflammatory mediators, to FGF-2 or to TGF-β. Equimolar concentrations of the 25 kDa heparin binding fragment of TSP-1 were even more efficient than the whole molecule, and promoted the angiogenic activity of FGF-2. On the contrary, the 140 kDa fragment of TSP-1 did not induce angiogenesis and turned off the angiogenic response to FGF-2. The 25 kDa fragment and TSP-1, but not the 140 kDa fragment, increased endothelial cell invasiveness and stimulated the production and activation of matrix metalloproteinase-2 (MMP-2). Moreover, the 25 kDa fragment reduced the synthesis of the MMP-2 inhibitor TIMP-2, while the 140 kDa fragment caused a twofold increase in TIMP-2 production and inhibited MMPs stimulation by TSP-1 and FGF-2. We conclude that TSP-1 is a source of smaller mediators of angiogenesis, which affect in an opposite way endothelial cell functions and proteolytic activity, thus resulting in an opposite final effect on angiogenesis.
2000
G., T., Morbidelli, L., Donnini, S., A., P., H. J., G., R., G., et al. (2000). The heparin binding 25kDa fragment of thrombospondin-1 promotes angiogenesis and modulates gelatinases and TIMP-2 in endothelial cells. THE FASEB JOURNAL, 14(12), 1674-1676.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/30108
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