Role of the latent TGF-β binding protein in the activation of latent TGF- β by co-cultures of endothelial and smooth muscle cells

R. Flaumenhaft, M. Abe, Y. Sato, K. Miyazono, J. Harpel, C. H. Heldin, D. B. Rifkin

Research output: Contribution to journalArticlepeer-review

210 Citations (Scopus)

Abstract

Transforming growth factor beta (TGF-β) is released from cells in a latent form consisting of the mature growth factor associated with an aminoterminal propeptide and latent TGF-β binding protein (LTBP). The endogenous activation of latent TGF-β has been described in co-cultures of endothelial and smooth muscle cells. However, the mechanism of this activation remains unknown. Antibodies to native platelet LTBP and to a peptide fragment of LTBP inhibit in a dose-dependent manner the activation of latent TGF-β normally observed when endothelial cells are cocultured with smooth muscle cells. Inhibition of latent TGF-β activation was also observed when cells were co-cultured in the presence of an excess of free LTBP. These data represent the first demonstration of a function for the LTBP in the extracellular regulation of TGF-β activity and indicate that LTBP participates in the activation of latent TGF-β, perhaps by concentrating the latent growth factor on the cell surface where activation occurs.

Original languageEnglish
Pages (from-to)995-1002
Number of pages8
JournalJournal of Cell Biology
Volume120
Issue number4
DOIs
Publication statusPublished - 1993

ASJC Scopus subject areas

  • Cell Biology

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