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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.

journal_name

Int J Mol Med

journal_title

International journal of molecular medicine

authors

Małgorzewicz S,Skrzypczak-Jankun E,Jankun J

doi

10.3892/ijmm.2013.1234

subject

Has Abstract

pub_date

2013-03-01 00:00:00

pages

503-10

issue

eissn

1107-3756

issn

1791-244X

journal_volume

pub_type

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Plasminogen activator inhibitor-1 in kidney pathology (Review).