Heparin-binding vitronectin up-regulates latent TGF-β production by bovine aortic endothelial cells

Academic Article

Abstract

  • Vitronectin, a serum and extracellular matrix protein, is present in vivo in two different conformations: a native form, which does not bind heparin, and a heparin-binding conformer, which results from interactions of native vitronectin with either the thrombin-antithrombin III complex or the terminal complement complex, C5b-9. We found that vitronectin stimulates the activity of the growth regulatory peptide, TGF-β, in the conditioned media of bovine aortic endothelial cells as a result of increased production of latent TGF-β. This effect is specific for the denatured, heparin-binding, form of vitronectin, since native vitronectin has no effect on the production of latent TGF-β by those cells. Stimulation is time and concentration-dependent, but is independent of protease activity. Stimulation is dependent on the presence of cells, since there was no increase in TGF-β activity observed when vitronectin was added to the conditioned media after removal from cells. Furthermore, incubation of recombinant latent TGF-β with vitronectin in a cell-free system does not result in increased TGF-β activity. Assays of total TGF-β levels in heat-treated conditioned media showed that vitronectin treatment elevates the levels of total TGF-β in the conditioned media. These results were further confirmed by western blot analysis of the conditioned media with antibodies specific for latent TGF-β. These data suggest that vitronectin regulates expression and/or secretion of TGF-β by bovine aortic endothelial cells. This cellular response to the heparin-binding form of vitronectin seems to be mediated by α(v)β3 integrins. Since in vivo situations in which heparin-binding vitronectin is present correlate well with those in which TGF-β activity is increased, we propose that vitronectin may be a significant regulator of TGF-β activity in vivo.
  • Published In

    Author List

  • Ribeiro SMF; Schultz-Cherry S; Murphy-Ullrich JE
  • Start Page

  • 1553
  • End Page

  • 1561
  • Volume

  • 108
  • Issue

  • 4