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Interaction of Angiogenesis Inhibitor TNP-470 with Basic Fibroblast Growth Factor Receptors

Authors
Journal
Journal of Surgical Research
0022-4804
Publisher
Elsevier
Publication Date
Volume
92
Issue
1
Identifiers
DOI: 10.1006/jsre.2000.5854
Keywords
  • Tnp-470
  • Agm-1470
  • Wound Healing
  • Basic Fibroblast Growth Factor
  • Basic Fibroblast Growth Factor Receptor
Disciplines
  • Biology

Abstract

Abstract TNP-470 is a synthetic analogue of fumagillin that acts as a potent angiogenesis inhibitor. Recently, our laboratory demonstrated that systemic administration of TNP-470 (5.0 mg/kg) decreased the rate of cutaneous wound healing by greater than 20%. In this study, we tested the hypothesis that TNP-470 interferes with the wound repair-stimulating action of basic fibroblast growth factor (bFGF) by competing with endogenous bFGF for its binding sites on the receptor protein. The influence of TNP-470 was examined in vitro in a ligand competition assay of high- and low-affinity receptor binding to 125I-bFGF in NIH/3T3 cells. Results demonstrated that recognition of 125I-bFGF by low-affinity growth factor binding sites was significantly decreased ( P < 0.01) in the presence of TNP-470. However, TNP-470 inhibition of radiolabeled bFGF binding to high-affinity sites was not significantly affected ( P = 0.07). In view of recent studies demonstrating that the low-affinity receptors of bFGF were heparan sulfate proteoglycans, we suggest that the influence of TNP-470 on diminished wound healing is due to its direct recognition by these molecules.

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