Thrombin-induced proliferation and expression of platelet-derived growth factor-A chain gene in human vascular smooth muscle cells

Chryso Kanthou, Graham Parry, Errol Wijelath, Vijay Vir Kakkar, Catherine Demoliou-Mason

Research output: Contribution to journalArticlepeer-review

63 Citations (Scopus)

Abstract

Treatment of human vascular smooth muscle cells (SMC) with human α-thrombin greatly increased DNA synthesis and cell proliferation. Both the integrity of the catalytic site and that of the anion binding exosite were required for expression of this activity. Experiments employing Northerns indicated induction of c-f{hook}os expression as well as a time-dependent induction of platelet-derived growth factor-A (PDGF-A) gene by thrombin. The thrombin mitogenic activity was potentiated by PDGF-BB, insulin and the vasoconstrictor peptide endothelin-1 suggesting synergism by convergence of intracellular growth-promoting signals. SMC treatment with pertussis toxin and forskolin indicated that the mitogenic activity of thrombin may be induced via signal transduction mechanism(s) involving changes in cAMP levels and activation of a Gi-like protein. These results suggest that thrombin may play a functional role in the regulation of human vascular SMC proliferation.

Original languageEnglish
Pages (from-to)143-148
Number of pages6
JournalFEBS Letters
Volume314
Issue number2
DOIs
Publication statusPublished - 14 Dec 1992

Keywords

  • Cyclic AMP
  • G protein
  • Pertussis toxin
  • Platelet-derived growth factor induction
  • Proliferation
  • Smooth muscle cell
  • Thrombin

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