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Urokinase and its receptors in chronic kidney disease

Guoqiang Zhang1, Allison A Eddy

  • 1University of Washington and Children's Hospital and Regional Medical Center, Division of Nephrology, 4800 Sand Point Way NE, Seattle, WA 98105, USA.

Frontiers in Bioscience : a Journal and Virtual Library
|May 30, 2008
PubMed

Insights

The urokinase system, including urokinase-type plasminogen activator (uPA) and its receptor (uPAR), plays complex roles in chronic kidney disease (CKD) progression, with site-specific effects influencing fibrosis and inflammation.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Cell Biology

Background:

  • The urokinase-type plasminogen activator (uPA) and its receptor (uPAR/CD87) are implicated in various physiological and pathological processes.
  • Their specific roles in chronic kidney disease (CKD) progression, particularly concerning organ- and site-specific effects, require detailed investigation.

Purpose of the Study:

  • To review the multifaceted roles of the uPA/uPAR system in the context of chronic kidney disease (CKD) progression.
  • To elucidate the organ- and site-specific actions of uPA and uPAR in renal pathophysiology.

Main Methods:

  • Literature review focusing on studies involving uPA and uPAR in experimental and clinical settings of CKD.
  • Analysis of data from uPA and uPAR knockout/deficient mouse models in experimental CKD.
  • Examination of cellular sources and signaling pathways involving uPA and uPAR in kidney disease.

Main Results:

  • uPA exhibits potential anti-fibrotic effects via hepatocyte growth factor activation and fibrinogen degradation, though its absence did not alter fibrosis in experimental CKD.
  • uPAR expression in renal cells and inflammatory cells is associated with anti-fibrotic effects, particularly through modulation of cell recruitment and migration.
  • Soluble uPAR, interactions with co-receptors, and alternative ligands like vitronectin contribute to uPAR's functional effects in kidney disease.

Conclusions:

  • The uPA/uPAR system has complex, site-specific roles in CKD, influencing fibrosis and inflammation through diverse mechanisms.
  • uPAR's primary impact in CKD appears to involve cell recruitment and migration, rather than direct anti-fibrotic action.
  • Understanding these intricate interactions is crucial for developing targeted therapies for CKD progression.

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