title: Plasminogen activator inhibitor-1 in kidney pathology (Review).
abstract: Plasminogen activator inhibitor type-1 (PAI-1) inhibits tissue plasminogen             activator (tPA) and urokinase plasminogen activator (uPA), which convert plasminogen             to plasmin, a strong proteolytic enzyme. Thus, PAI-1 is a primary and negative             regulator of plasmin-driven proteolysis. In addition to its main role as an inhibitor             of fibrinolysis, PAI‑1 has been implicated as a mediator in other processes, including             fibrosis, rheumatoid arthritis, atherosclerosis, tumor angiogenesis and bacterial             infections. It also significantly modulates cellular adhesion or migration, wound             healing, angiogenesis and tumor cell metastasis. However, in the present study,             we have reviewed the literature in relation to different kidney diseases where             PAI-1 regulates fibrinolysis and acts independently of proteolysis. PAI-1 is normally             produced in trace amounts in healthy kidneys but is synthesized in a wide variety             of both acute and chronic diseased kidneys. We reviewed the role of PAI-1 in diabetic             kidney nephropathy, chronic kidney disease, hemodialysis, peritoneal dialysis             and in kidney transplantation. Increased PAI-1 expression results in accumulation             of extracellular matrix (ECM) leading to numerous kidney diseases. Predisposition             to some diseases is due to the genetic role of PAI-1 in their development. A number             of studies demonstrated that the inhibition of PAI-1 activity or therapy with             a mutant PAI-1 increases matrix turnover and reduces glomerulosclerosis by competing             with endogenous PAI-1. This strongly suggests that PAI-1 is a valid target in             the treatment of fibrotic renal disease. However, net proteolytic activity depends             on the delicate balance between its negative regulation by PAI-1 and activation             by uPA and tPA. Also, plasmin activated by its inhibitors upregulates activity             of other enzymes. Thus, assessment of prognosis for the diseased kidney should             include a variety of proteolysis regulators and enzymes.
authors: Department of Clinical Nutrition, Medical University of Gdańsk,                     Gdańsk 80-211, Poland.
authors: Sylwia
authors: S
authors: Małgorzewicz
authors: Ewa
authors: E
authors: Skrzypczak-Jankun
authors: Jerzy
authors: J
authors: Jankun
mesh_terms: D000818:Animals; D003928:Diabetic Nephropathies / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005342:Fibrinolysis; D006801:Humans; D007668:Kidney / Q000473:pathology*; D016030:Kidney Transplantation; D010530:Peritoneal Dialysis; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D059748:Proteolysis; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000037:antagonists & inhibitors; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors
chemical_list: D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator