Thromboxane a2 modulates the fibrinolytic system in glomerular
mesangial cells.
Coffman, Thomas M., Robert F. Spurney, Roslyn B. Mannon, & Richard
Levenson.
Departments of Medicine and Pathology, Duke University and Durham
VA Medical Centers, Durham, NC.
APStracts 5:0100F, 1998.
We examined the effects of thromboxane (TX) A2 on the activities of
the plasminogen-plasmin system in glomerular mesangial cells. When
mesangial cells are exposed to the TXA2 agonist U46619, a substantial
increase in production of plasminogen activator inhibitor-1 (PAI-1)
protein is observed that is significantly greater than that induced
by 10% serum alone. This increase in PAI-1 protein production is
accompanied by an increase in steady state levels of PAI-1 mRNA. This
stimulation is specifically mediated by TXA2 (TP) receptors since
U46619 also stimulates PAI-1 expression in cells that are transfected
with TP receptors and this stimulation of PAI-1 production is
completely blocked by the TXA2 receptor antagonist, SQ-29,548.
Despite the increase in PAI-1 production, there was net stimulation
of plasmin activity in the medium of mesangial cells that had been
exposed to U46619. Furthermore, U46619 also caused an increase in
tissue plasminogen activator (tPA) mRNA levels. Thus, thromboxane A2
stimulates the production of PAI-1 and plasminogen activators by
mesangial cells through a receptor-dependent mechanism. In
inflammatory renal diseases, the balance of these effects may
modulate glomerular thrombosis and renal fibrosis.
Received 1 December 1997; accepted in final form 13 May 1998.
APS Manuscript Number F371-7.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 16 June 1998