Abstract
Latent transforming growth factor-β (TGF-β) is activated when endothelial cells (ECs) and smooth muscle cells (SMCs) are in contact. This activation requires plasminogen activator (PA) activity on ECs and the binding of latent TGF-β to SMCs. Since SMCs are not always in contact with ECs in the vascular wall, a mechanism for the activation of latent TGF-β in homotypic SMCs needs to be elucidated. A low-dose of TGF-β1 10∼~100 pg/ml) stimulated the proliferation of porcine aortic SMCs (PASMCs), while a high-dose of TGF-β1 (1,000 pg/ml) inhibited proliferation. Exogenous urokinase-type PA (uPA) enhanced the proliferation of PASMCs, and the stimulatory effect of uPA was comparable with that of low-dose TGF-β1. The effect of uPA on the proliferation of PASMCs was blocked by a co-administration of either neutralizing anti-TGF-β antibody or α2 plastmin inhibitor, suggesting that exogenous uPA generates active TGF-β via plasmin activity. A binding experiment using 125I-uPA showed that PASMCs expressed specific receptors for uPA. The 2 hr incubation of PASMCs with uPA increased the cell-associated uPA activity. When PASMCs were washed after incubation under the same conditions, the stimulatory effect of uPA on the proliferation of PASMCs persisted. Thus, receptor-bound uPA has been found to be involved in this reaction. The stimulatory effect of uPA on the proliferation of PASMCs was abrogated by the monoclonal antibody against latency-associated peptide, which inhibits the binding of latent TGF-β to PASMCs. These results indicate that the simultaneous bindings of uPA and latent TGF-β generates active TGF-β in homotypic SMCs.
Original language | English |
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Pages (from-to) | 23-34 |
Number of pages | 12 |
Journal | Tohoku Journal of Experimental Medicine |
Volume | 179 |
Issue number | 1 |
DOIs | |
Publication status | Published - 1996 May |
Keywords
- Activation
- Latent TGF-β
- Smoth muscle cell
- uPA
- uPA receptor
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)