Role of the Latent TGF-β Binding Protein in the Activation of Latent TGF-β by Co-Cultures of Endothelial and Smooth Muscle Cells

• Published in: The Journal of cell biology Vol. 120; no. 4; pp. 995 - 1002
• Main Authors: Flaumenhaft, Robert, Abe, Mayumi, Sato, Yasufumi, Miyazono, Kohei, Harpel, John, Heldin, Carl-Henrik, Rifkin, Daniel B.
• Format: Journal Article
• Language: English
• Published: New York, NY Rockefeller University Press 01-02-1993; The Rockefeller University Press
• Subjects: Analytical, structural and metabolic biochemistry; Animals; Antibodies; Biological and medical sciences; Carrier Proteins - metabolism; Cattle; Cell growth; Cells; Cells, Cultured; Coculture techniques; Culture Media; Cultured cells; Endothelial cells; Endothelium, Vascular - cytology; Endothelium, Vascular - metabolism; Fibrinolysin - metabolism; Fundamental and applied biological sciences. Psychology; Granulosa cells; Human growth; In Vitro Techniques; Intracellular Signaling Peptides and Proteins; Latent TGF-beta Binding Proteins; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - metabolism; Platelets; Protein hormones. Growth factors. Cytokines; Protein Precursors - metabolism; Proteins; Transforming Growth Factor beta - metabolism; Transforming growth factors; Cell culture; Binding protein; Mixed cell culture; Cell line; Transforming growth factor; Striated muscle; Endothelium; Latency
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.120.4.995

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.