Table 2.

Manipulation of PAI-1 and serine proteases in experimental kidney diseasesa

Genetic or Therapeutic ManipulationReduced FibrosisIncreased FibrosisNo Change in Fibrosis
PAI-1−/−Crescentic anti-GBM nephritis (28)Passive anti-GBM nephritis (30)
Streptozotocin-induced diabetes (43,44)
db/db diabetes (44)
5/6 nephrectomy (55)
Protein overload (60)
Obstructive nephropathy (61)
TGF-β transgenic mice (63)
PAI-1 overexpressing miceCrescentic anti-GBM nephritis (28)
Obstructive nephropathy (62)
PAI-1 mutantAnti–Thy-1 nephritis (37)
PAI-1 neutralizing antibodyLPS-induced endotoxemia (152)
Plasminogen−/− miceObstructive nephropathy (93,95)Crescentic anti-GBM nephritis (29)
tPA−/− miceObstructive nephropathy (87)Crescentic anti-GBM nephritis (29)
tPA recombinant proteinCrescentic anti-GBM nephritis (153)
Anti–Thy-1 nephritis (36)
uPA−/−Crescentic anti-GBM nephritis (28)
Obstructive nephropathy (109)
uPAR−/− miceObstructive nephropathy (71)Crescentic anti-GBM nephritis (28)
  • a db/db, spontaneously diabetic mouse as a result of a genetic mutation in the leptin receptor; GBM, glomerular basement membrane; tPA, tissue-type plasminogen activator; uPA, urokinase-type plasminogen activator; uPAR, uPA receptor.