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Thrombin‐induced proliferation and expression of platelet‐derived growth factor‐A chain gene in human vascular smooth muscle cells
Author(s) -
Kanthou Chryso,
Parry Graham,
Wijelath Errol,
Kakkar Vijay Vir,
Demoliou-Mason Catherine
Publication year - 1992
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(92)80961-f
Subject(s) - thrombin , vascular smooth muscle , growth factor , thrombin generation , gene , platelet derived growth factor , gene expression , microbiology and biotechnology , platelet , cell growth , endocrinology , biology , smooth muscle , platelet derived growth factor receptor , medicine , chemistry , immunology , biochemistry , receptor
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‐ƒ 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 G i ‐like protein. These results suggest that thrombin may play a functional role in the regulation of human vascular SMC proliferation.