PAI-1 deficiency attenuates the fibrogenic response to ureteral obstruction

摘要: PAI-1 deficiency attenuates the fibrogenic response to ureteral obstruction . Background Progressive renal disease is characterized by induction of plasminogen activator inhibitor-1 (PAI-1), suggesting that impaired activity plasmin cascade may play a role in fibrosis. Methods To test this hypothesis, severity fibrosis caused unilateral (UUO) was compared wild-type (+/+) and deficient (-/-) mice. The extent interstitial inflammation fibrosis, activity, expression profibrotic genes evaluated after 3, 7, 14 days UUO. Results Renal mRNA levels increased 8- 16-fold +/+ mice UUO surgery, protein detected kidney homogenates. Interstitial significantly attenuated -/- with at day 7 14, based on area stained picrosirius red total collagen content. However, neither mean nor activities were number macrophages lower three seven UUO; myofibroblasts fewer days. At same time points, altered cellularity associated significant reduction for transforming growth factor-β procollagens α1(I) α1(III). Conclusions These studies establish an important response. results demonstrate one fibrosis-promoting function its recruitment fibrosis-inducing cells, including macrophages.