PLASMINOGEN ACTIVATOR INHIBITOR-1 AND TISSUE-TYPE PLASMINOGEN ACTIVATOR ARE UP-REGULATED DURING UNILATERAL URETERAL OBSTRUCTION IN ADULT RATS

Purpose: The plasminogen activator (PA)-plasmin system has been shown to influence turnover of the extracellular matrix in various tissues. We examined the alteration of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA) in kidneys with unilateral ureteral obstruction in rats.Materials and Methods: Female rats that underwent ligation of the left ureter were sacrificed 12 hours, 1, 5 or 10 days later. The expressions of PAI-1 and t-PA was determined by reverse transcription-polymerase chain reaction and immunohistochemical studies in the obstructed and contralateral kidneys in each group.Results: Control kidneys showed no PAI-1 messenger (m)RNA expression. After days 1 through 10 of unilateral ureteral obstruction the amount of PAI-1 mRNA significantly increased in obstructed compared with contralateral kidneys (p < 0.01). Meanwhile, slight polymerase chain reaction products of t-PA were observed in control kidneys. After 12 hours through 10 days of unilateral ureteral obstruction, t-PA mRNA in obstructed and contralateral kidneys was significantly elevated compared with in control kidneys (p < 0.05). No significant difference in t-PA was observed in the obstructed and contralateral kidneys in each group. Immunoreactivity to PAI-1 and t-PA was identified in obstructed kidneys.Conclusions: PAI-1 and t-PA are up-regulated in obstructed rat kidneys. Our results indicate that the PA-plasmin system has a role in the process of matrix accumulation and degradation during rat obstructive nephropathy.