Thromboxane A2modulates the fibrinolytic system in glomerular mesangial cells.

Journal Article (Journal Article)

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 TxA2agonist 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 TxA2receptor 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 TxA2stimulates 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.

Full Text

Duke Authors

Cited Authors

  • Coffman, TM; Spurney, RF; Mannon, RB; Levenson, R

Published Date

  • August 1, 1998

Published In

Volume / Issue

  • 275 / 2

Start / End Page

  • F262 - F269

PubMed ID

  • 29586047

Electronic International Standard Serial Number (EISSN)

  • 1522-1466

Digital Object Identifier (DOI)

  • 10.1152/ajprenal.1998.275.2.F262


  • eng

Conference Location

  • United States