Thrombospondin 1 does not activate transforming growth factor β1 in a chemically defined system or in smooth-muscle-cell cultures

D. J. Grainger, E. K. Frow

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

The cytokine transforming growth factor β1 (TGF-β1) is secreted in a latent form that has no known biological activity. The conversion of latent TGF-β1 into its biologically active 25 kDa form is thought to be an important step in the regulation of TGF-β activity both in cell culture and in vivo. Thrombospondin (TSP)-1, a 360 kDa platelet α-granule and extracellular matrix protein, has been shown to participate in TGF-β1 activation. We have used a chemically defined system to examine the mechanism of TSP-1-mediated TGF-β1 activation. However, the addition of two different preparations of TSP-1 to recombinant small latent TGF-β1 in the test tube resulted in only a very small increase in the proportion of the TGF-β1 able to bind to the TGF-β type II receptor: from 0.1% to a maximum of 0.4 %. This small effect was not specific for TSP-1: matrix metalloproteinase 2, tissue inhibitor of matrix metalloproteinase 2 and active plasminogen activator inhibitor 1, but not transglutaminase, human serum albumin or immunoglobulin, had quantitatively similar effects on latent TGF-β1. Furthermore, no change in the activity associated with small latent TGF-β1 was noted in either mink lung epithelial cell or rat aortic smooth-muscle cell culture systems in. the presence of TSP-1 (or TSP-1-derived peptides). We conclude that TSP-1, either alone or in the presence of cultured smooth-muscle cells (a cell type known to activate latent TGF-β invitro and in vivo) is unable to activate latent TGF-β1. Any TSP-mediated activation of TGF-β1 must depend on additional factor(s) not present in our systems.

Original languageEnglish (US)
Pages (from-to)291-298
Number of pages8
JournalBiochemical Journal
Volume350
Issue number1
DOIs
StatePublished - Aug 15 2000
Externally publishedYes

Keywords

  • Cytokine
  • Fibroblast
  • Platelet
  • Wound healing

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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