TY - JOUR
T1 - Thromboxane A2 modulates the fibrinolytic system in glomerular mesangial cells
AU - Coffman, Thomas M.
AU - Spurney, Robert F.
AU - Mannon, Roslyn B.
AU - Levenson, Richard
PY - 1998/8
Y1 - 1998/8
N2 - 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.
AB - 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.
KW - Glomerulonephritis
KW - Plasminogen activator inhibitor-1
KW - Thromboxane receptor
KW - Tissue plasminogen activator
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U2 - 10.1152/ajprenal.1998.275.2.f262
DO - 10.1152/ajprenal.1998.275.2.f262
M3 - Article
C2 - 9691017
AN - SCOPUS:0032132754
VL - 275
SP - F262-F269
JO - American Journal of Physiology - Renal Physiology
JF - American Journal of Physiology - Renal Physiology
SN - 0363-6127
IS - 2 44-2
ER -