The mechanism for the activation of latent TGF-β during co-culture of endothelial cells and smooth muscle cells: Cell-type specific targeting of latent TGF-β to smooth muscle cells

Y. Sato, F. Okada, M. Abe, T. Seguchi, M. Kuwano, S. Sato, A. Furuya, N. Hanai, T. Tamaoki

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91 Citations (Scopus)

Abstract

Transforming growth factor-β (TGF-β) is secreted in a latent form and activated during co-culture of endothelial cells and smooth muscle cells. Plasmin located on the surface of endothelial cells is required for the activation of latent TGF-β (LTGF-β) during co-culture, and the targeting of LTGF-β to the cellular surface is requisite for its activation. In the present study, the cellular targeting of LTGF-β was examined. We detected the specific binding of 125I-large LTGF-β1 isolated from human platelets to smooth muscle cells but not to endothelial cells. A mAb against the latency-associated peptide (LAP) of large LTGF-β1 complex, which blocked the binding of 125I-large LTGF-β1 to smooth muscle cells, inhibited the activation of LTGF-β during co-culture. The binding of 125I-large LTGF- β1 could not be competed either by mannose-6-phosphate (300 μM) or by the synthetic peptide Arg-Gly-Asp-Ser (300 μg/ml). These results indicate that the targeting of LTGF-β to smooth muscle cells is required for the activation of LTGF-β during co-culture of endothelial cells and smooth muscle cells. The targeting of LTGF-β to smooth muscle cells is mediated by LAP, and the domain of LAP responsible for the targeting to smooth muscle cells may not be related to mannose-6-phosphate or an Arg-Gly-Asp sequence, both of which have been previously proposed as candidates for the cellular binding domains within LAP.

Original languageEnglish
Pages (from-to)1249-1254
Number of pages6
JournalJournal of Cell Biology
Volume123
Issue number5
DOIs
Publication statusPublished - 1993

ASJC Scopus subject areas

  • Cell Biology

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