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Macrophage Function Modulated by tPA Signaling in Mouse Experimental Kidney Disease Models.

Ling Lin1, Kebin Hu1,2

  • 1Division of Nephrology, Department of Medicine, Penn State University College of Medicine, Hershey, PA 17033, USA.

International Journal of Molecular Sciences
|July 14, 2023
PubMed
Summary

Tissue plasminogen activator (tPA) influences macrophage behavior in chronic kidney disease. This review explores how tPA signaling impacts kidney inflammation and fibrosis.

Keywords:
annexin A2inflammationkidney diseaselow-density lipoprotein receptor-related protein (LRP-1)macrophage functionmacrophage polarizationnuclear factor- κB (NF-κB)signal transductiontissue plasminogen activator (tPA)

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Area of Science:

  • Nephrology
  • Immunology
  • Biochemistry

Background:

  • Macrophage infiltration is central to chronic kidney disease (CKD) pathogenesis.
  • Tissue plasminogen activator (tPA) is a serine protease involved in coagulation, fibrinolysis, and matrix degradation.
  • tPA also functions as a cytokine, modulating cellular signaling pathways.

Purpose of the Study:

  • To review the current understanding of tPA's role in modulating macrophage function.
  • To explore the signaling mechanisms underlying tPA's effects on macrophages in kidney injury.
  • To connect tPA-modulated macrophage function to kidney fibrosis and inflammation.

Main Methods:

  • Literature review of studies on tPA, macrophages, and kidney disease.
  • Analysis of signaling pathways involved in tPA-macrophage interactions.
  • Synthesis of findings related to kidney fibrosis and inflammation.

Main Results:

  • tPA significantly influences macrophage recruitment, activation, and polarization in the kidney.
  • tPA activates specific intracellular signaling cascades (e.g., MAPK, NF-κB) in macrophages.
  • These tPA-driven macrophage responses contribute to the progression of kidney fibrosis and inflammation.

Conclusions:

  • tPA plays a critical role in orchestrating macrophage responses during kidney injury.
  • Targeting tPA-mediated signaling pathways presents a potential therapeutic strategy for CKD.
  • Further research is needed to fully elucidate tPA's complex role in kidney disease.