Lise Wogensen

Plasminogen activator inhibitor-1 gene deficiency attenuates TGF-β1-induced kidney disease

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Background. Transforming growth factor-β1 (TGF-β1) stimulates the deposition of extracellular matrix (ECM), which is a hallmark in end-stage renal disease. The importance of TGF-β1 - induced changes in protease activity in this process is not fully elucidated. TGF-β1 up-regulates plasminogen activator inhibitor type 1 (PAI-1), which lowers matrix degradation. Our aim was to investigate the importance of PAI-1 in TGF-β1 - induced kidney disease. Methods. TGF-β1 transgenic mice were bred with PAI-1 gene deficient mice. The effect of PAI-1 gene knockout on TGF-β1 - induced glomerular disease was investigated by measuring morphologic changes in the glomeruli. Interstitial changes were assessed by measurement of total collagen content and expression and localization of ECM components. Finally, protease activity was evaluated by plasmin activity measurement and by gel and in situ gelatin zymography. Results. TGF-β1 elevated PAI-1 expression fourfold. PAI-1 gene deficiency attenuated the TGF-β1 - induced mesangial expansion and basement membrane thickening. Furthermore, PAI-1 knockout diminished collagen accumulation in TGF-β1 - positive mice. The expression of both collagen type I and III were reduced. Interestingly, no difference in protease activity could be ascertained as cause of the decreased ECM accumulation. Conclusion. We show that PAI-1 gene deficiency attenuates TGF-β1 - induced kidney disease, decreasing both glomerular and interstitial ECM deposition. Thus, PAI-1 mediates some of the biological effects of TGF-β1 in vivo. However, we could not find evidence supporting the notion that the effect was mediated through increased protease activity.

BogserieKidney International
Sider (fra-til)2651-2666
Antal sider16
StatusUdgivet - 1 dec. 2005

Se relationer på Aarhus Universitet Citationsformater

ID: 156885316