Role of the latent TGF-beta binding protein in the activation of latent TGF-beta by co-cultures of endothelial and smooth muscle cells.
Transforming growth factor beta (TGF-beta) is released from cells in a latent form consisting of the mature growth factor associated with an aminoterminal propeptide and latent TGF-beta binding protein (LTBP). The endogenous activation of latent TGF-beta 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-beta normally observed when endothelial cells are cocultured with smooth muscle cells. Inhibition of latent TGF-beta 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-beta activity and indicate that LTBP participates in the activation of latent TGF-beta, perhaps by concentrating the latent growth factor on the cell surface where activation occurs.
Flaumenhaft
R
R
Department of Cell Biology, New York University Medical Center, New York 10016.
Abe
M
M
Sato
Y
Y
Miyazono
K
K
Harpel
J
J
Heldin
C H
CH
Rifkin
D B
DB
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D003470:Culture Media; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005341:Fibrinolysin / Q000378:metabolism; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D053779:Latent TGF-beta Binding Proteins; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D002352:Carrier Proteins; D003470:Culture Media; D047908:Intracellular Signaling Peptides and Proteins; D053779:Latent TGF-beta Binding Proteins; D011498:Protein Precursors; D016212:Transforming Growth Factor beta; D005341:Fibrinolysin