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International Journal of Molecular Medicine
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Review

Plasminogen activator inhibitor-1 in kidney pathology (Review)

  • Authors:
    • Sylwia Małgorzewicz
    • Ewa Skrzypczak-Jankun
    • Jerzy Jankun
  • View Affiliations / Copyright

    Affiliations: Department of Clinical Nutrition, Medical University of Gdańsk, Gdańsk 80-211, Poland, Urology Research Center, Department of Urology, College of Medicine, University of Toledo, Toledo, OH 43614, USA
  • Pages: 503-510
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    Published online on: January 10, 2013
       https://doi.org/10.3892/ijmm.2013.1234
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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.
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Copy and paste a formatted citation
Spandidos Publications style
Małgorzewicz S, Skrzypczak-Jankun E and Jankun J: Plasminogen activator inhibitor-1 in kidney pathology (Review). Int J Mol Med 31: 503-510, 2013.
APA
Małgorzewicz, S., Skrzypczak-Jankun, E., & Jankun, J. (2013). Plasminogen activator inhibitor-1 in kidney pathology (Review). International Journal of Molecular Medicine, 31, 503-510. https://doi.org/10.3892/ijmm.2013.1234
MLA
Małgorzewicz, S., Skrzypczak-Jankun, E., Jankun, J."Plasminogen activator inhibitor-1 in kidney pathology (Review)". International Journal of Molecular Medicine 31.3 (2013): 503-510.
Chicago
Małgorzewicz, S., Skrzypczak-Jankun, E., Jankun, J."Plasminogen activator inhibitor-1 in kidney pathology (Review)". International Journal of Molecular Medicine 31, no. 3 (2013): 503-510. https://doi.org/10.3892/ijmm.2013.1234
Copy and paste a formatted citation
x
Spandidos Publications style
Małgorzewicz S, Skrzypczak-Jankun E and Jankun J: Plasminogen activator inhibitor-1 in kidney pathology (Review). Int J Mol Med 31: 503-510, 2013.
APA
Małgorzewicz, S., Skrzypczak-Jankun, E., & Jankun, J. (2013). Plasminogen activator inhibitor-1 in kidney pathology (Review). International Journal of Molecular Medicine, 31, 503-510. https://doi.org/10.3892/ijmm.2013.1234
MLA
Małgorzewicz, S., Skrzypczak-Jankun, E., Jankun, J."Plasminogen activator inhibitor-1 in kidney pathology (Review)". International Journal of Molecular Medicine 31.3 (2013): 503-510.
Chicago
Małgorzewicz, S., Skrzypczak-Jankun, E., Jankun, J."Plasminogen activator inhibitor-1 in kidney pathology (Review)". International Journal of Molecular Medicine 31, no. 3 (2013): 503-510. https://doi.org/10.3892/ijmm.2013.1234
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