Title: Involvement of u-PA in the anti-apoptotic activity of TGFbeta for vascular smooth muscle cells
Authors: Herbert, J M ×
Carmeliet, Peter #
Issue Date: Oct-1997
Series Title: FEBS Letters vol:413 issue:3 pages:401-4
Abstract: Previous studies suggest a role for the plasminogen or fibrinolytic system in the activation of latent-transforming growth beta (L-TGFbeta) into active TGFbeta. In the present study, the anti-apoptotic activity of TGFbeta on cultured vascular smooth muscle cells (SMC) isolated from the aorta of transgenic mice with single inactivation of genes encoding the tissue-type plasminogen activator (t-PA(-/-)), urokinase-type plasminogen activator (u-PA(-/-)), urokinase receptor (u-PAR(-/-)) or plasminogen (Plg(-/-)) genes was examined. Latent-TGFbeta inhibited serum deprivation-induced apoptosis of SMC isolated from wild-type and t-PA(-/-) mice but failed to reduce apoptosis of SMC isolated from u-PA(-/-), u-PAR(-/-) or Plg(-/-) mice. Active TGFbeta, however, was able to inhibit serum deprivation-induced apoptosis of these 5 cell types, indicating that u-PA and/or plasmin were involved in the activation of L-TGFbeta. The anti-apoptotic effect of L-TGFbeta could not be evoked by addition of exogenous t-PA to u-PA(-/-) cells, but was revealed by addition of exogenous u-PA or plasmin. This effect was dependent on the catalytic activity of plasmin as revealed by the dose-dependent inhibition of aprotinin or epsilon aminocaproic acid (EACA). These results therefore indicate that, at least in vitro, u-PA-mediated plasmin, through the generation of active TGFbeta from L-TGFbeta, is required for the anti-apoptotic activity of TGFbeta on SMC.
ISSN: 0014-5793
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular and Vascular Biology
Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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