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Annexin A2 interferes with complement regulation within the glomerulus.

Brandon Renner1, Jennifer Laskowski1, Felix Poppelaars1

  • 1Department of Medicine, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado, USA.

The Journal of Biological Chemistry
|September 1, 2025
PubMed
Summary
This summary is machine-generated.

Annexin A2 interferes with Factor H function, increasing complement-driven kidney injury. Its absence protects against injury, suggesting Annexin A2 promotes kidney inflammation in disease.

Keywords:
Annexin A2complementfactor Hinflammationkidney

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Area of Science:

  • Immunology
  • Nephrology
  • Molecular Biology

Background:

  • The alternative pathway of complement is a key factor in glomerular diseases.
  • Factor H is crucial for kidney protection against complement-mediated injury.
  • Other proteins can disrupt Factor H regulation, leading to kidney damage.

Purpose of the Study:

  • To investigate the role of Annexin A2 in Factor H function and kidney injury.
  • To determine how extracellular Annexin A2 affects complement regulation in kidney cells.

Main Methods:

  • In vitro and in vivo experiments assessing Annexin A2 binding to Factor H.
  • Analysis of Factor H's complement regulatory activity on glomerular cells and extracellular vesicles.
  • Studies using Annexin A2-deficient mice to evaluate kidney injury models.

Main Results:

  • Extracellular Annexin A2 binds to Factor H (SCR6-8), impairing its regulatory function on glomerular endothelial cells and podocytes.
  • Annexin A2 does not affect Factor H function on extracellular matrix or erythrocytes.
  • Targeted deletion of Annexin A2 in mice reduced cyclosporine-induced kidney injury and complement activation.
  • Annexin A2 expression is increased in kidney disease states.

Conclusions:

  • Extracellular Annexin A2 acts as a positive regulator of complement activation in the kidney.
  • Annexin A2 promotes kidney inflammation and injury by inhibiting Factor H's protective function.
  • Annexin A2 is a potential therapeutic target for glomerular diseases.