Simultaneous bindings of uPA and latent TGF-β for the activation of latent TGF-β in homotypic smooth muscle cells

Hiroko Abe, Mayumi Abe, Katsuhiro Tanaka, Chika Iwasaka, Yasufumi Sato

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

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 languageEnglish
Pages (from-to)23-34
Number of pages12
JournalTohoku Journal of Experimental Medicine
Volume179
Issue number1
DOIs
Publication statusPublished - 1996 May

Keywords

  • Activation
  • Latent TGF-β
  • Smoth muscle cell
  • uPA
  • uPA receptor

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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