Transforming growth factor-beta complexes with thrombospondin.
- 1 February 1992
- journal article
- Published by American Society for Cell Biology (ASCB) in Molecular Biology of the Cell
- Vol. 3 (2) , 181-188
- https://doi.org/10.1091/mbc.3.2.181
Abstract
Thrombospondin (TSP) was demonstrated to inhibit the growth of bovine aortic endothelial cells, an activity that was not neutralized by antibodies to TSP or by other agents that block TSP-cell interactions but that partially was reversed by a neutralizing antibody to transforming growth factor-beta (TGF-beta). Similar to TGF-beta, TSP supported the growth of NRK-49F colonies in soft agar in a dose-dependent manner, which required epidermal growth factor and was neutralized by anti-TGF-beta antibody. Chromatography of a TSP preparation did not separate the TGF-beta-like NRK colony-forming activity from high molecular weight protein. However, when chromatography was performed at pH 11, this activity was dissociated from TSP. These results suggest that at least some growth modulating activities of TSP are due to TGF-beta associated with TSP by strong non-covalent forces. Most of the active TGF-beta released from platelets after degranulation was associated with TSP, as demonstrated by anti-TSP immunoaffinity and gel permeation chromatography. 125I-TGF-beta binds to purified TSP in an interaction that is specific in the sense that bound TGF-beta could be displaced by TGF-depleted TSP but not significantly by native TSP, heparin, decorin, alpha 2-macroglobulin, fibronectin, or albumin. Hence, TGF-beta can bind to TSP, and the complex forms under physiological conditions. Furthermore, TSP-associated TGF-beta is biologically active, and the binding of TGF-beta to TSP may protect TGF-beta from extracellular inactivators.Keywords
This publication has 26 references indexed in Scilit:
- Specific inhibition of endothelial cell proliferation by thrombospondinBiochemical and Biophysical Research Communications, 1990
- Mechanism of activation of latent recombinant transforming growth factor beta 1 by plasmin.The Journal of cell biology, 1990
- Physiology of ThrombospondinAnnual Review of Medicine, 1990
- Transforming growth factor‐β1 binds to immobilized fibronectinJournal of Cellular Biochemistry, 1989
- Transforming growth factor beta increases cell surface binding and assembly of exogenous (plasma) fibronectin by normal human fibroblasts.Molecular and Cellular Biology, 1988
- Cell surface thrombospondin is functionally essential for vascular smooth muscle cell proliferationThe Journal of cell biology, 1988
- Inhibitory action of transforming growth factor beta on endothelial cells.Proceedings of the National Academy of Sciences, 1987
- Thrombospondin: a modular adhesive glycoprotein of platelets and nucleated cells.The Journal of cell biology, 1987
- Control of smooth muscle cell growth by components of the extracellular matrix: autocrine role for thrombospondin.Proceedings of the National Academy of Sciences, 1986
- Cultured human fibroblasts synthesize and secrete thrombospondin and incorporate it into extracellular matrix.Proceedings of the National Academy of Sciences, 1983