Vol. 275, Issue 2, F262-F269, August 1998
Thromboxane A2 modulates the
fibrinolytic system in glomerular mesangial cells
Thomas M.
Coffman1,
Robert F.
Spurney1,
Roslyn B.
Mannon1, and
Richard
Levenson2
Departments of 1 Medicine and
2 Pathology, Duke University and
Durham Veterans Affairs Medical Center, Durham, North Carolina
27705
We examined the
effects of thromboxane A2
(TxA2) on the activities of
the plasminogen-plasmin system in glomerular mesangial cells. When mesangial cells are exposed to the
TxA2 agonist U-46619, 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 (thromboxane prostanoid,
TP) receptors, since U-46619 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 U-46619. Furthermore, U-46619 also caused an
increase in tissue plasminogen activator (tPA) mRNA levels. Thus
TxA2 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.
plasminogen activator inhibitor-1; tissue plasminogen activator; thromboxane receptor; glomerulonephritis
