Original ArticlesRegulation of plasminogen activator inhibitor-1 secretion by growth factors in smooth muscle cellsLau, H. K. F.; Ho, J.Author Information The authors are with the Division of Hematology, Department of Medicine, and Department of Laboratory Medicine and Pathobiology, St Michael's Hospital and University of Toronto, Toronto, Ontario, Canada. (Received 19 December 2001; revised 16 April 2002; accepted 22 April 2002) Sponsorship: This project was funded by the St Michael's Hospital Research Society. Address correspondence to Dr Herbert Lau, Room 2-015, St Michael's Hospital, 30 Bond Street, Toronto, Ontario M5B 1W8, Canada. Tel: (+1) 416 864 5522; fax: (+1) 416 864 5294; e-mail address: firstname.lastname@example.org Blood Coagulation & Fibrinolysis: September 2002 - Volume 13 - Issue 6 - p 541-549 Buy Abstract Epithelioid-type vascular smooth muscle cells are metabolically active and secrete many proteases and protease inhibitors. We have previously cloned epithelioid-type smooth muscle cells from rat carotid arteries, and showed that polypeptide growth factors basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) could dose-dependently induce plasminogen activator inhibitor-1 (PAI-1) secretion from these cells. In the present study, we have used these cells to investigate the growth factor-induced signal transduction pathways leading to PAI-1 secretion. We report here that PAI-1 induction was dependent on protein kinase C (PKC) and tyrosine kinase but not on protein kinase A (PKA), ras and phosphoinositol-3-kinase inhibitor. Induction of PAI-1 by bFGF and PDGF was also accompanied by activation of a mitogen-activated protein kinase pathway involving Raf/Mek/Erk1/2, and the srcp family non-receptor tyrosine kinases. Syk, another non-receptor tyrosine kinase, on the contrary, behaved differently from src in that it was part of a pathway leading to PAI-1 induction by bFGF, but not when PDGF was used as the stimulating reagent. Activation of a PKA-dependent pathway(s) opposed PAI-1 induction. One mechanism for PKA activators to inhibit PAI-1 secretion was that they markedly inhibited the phosphorylations of Mek and mitogen-activated protein kinase that were up-regulated in the presence of bFGF and PDGF. © 2002 Lippincott Williams & Wilkins, Inc.