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Related Experiment Videos

Decrease of heparan sulfate staining in the glomerular basement membrane in murine lupus nephritis

M C van Bruggen1, K Kramers, M N Hylkema

  • 1Department of Nephrology, University Hospital Nijmegen, The Netherlands.

The American Journal of Pathology
|March 1, 1995
PubMed
Summary

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Lupus nephritis causes a loss of heparan sulfate (HS) staining in the glomerular basement membrane (GBM), linked to increased albuminuria. This loss may be due to immunoglobulin (Ig) deposits masking HS, not a reduction in overall HS content.

Area of Science:

  • Nephrology
  • Immunology
  • Biochemistry

Background:

  • Lupus nephritis is characterized by glomerular damage and proteinuria.
  • Heparan sulfate (HS) is a crucial component of the glomerular basement membrane (GBM), maintaining its filtration barrier function.
  • Previous studies observed a loss of HS staining in human lupus nephritis biopsies.

Purpose of the Study:

  • To investigate the relationship between HS staining in the GBM and albuminuria in a mouse model of lupus nephritis (MRL/lpr mice).
  • To determine if the observed loss of HS staining is associated with changes in other extracellular matrix components or overall HS content.
  • To explore potential mechanisms, such as immunoglobulin (Ig) deposition, contributing to HS loss.

Main Methods:

  • MRL/lpr mice with varying durations of albuminuria (<7 days and 14-21 days) and non-albuminuric age-matched controls were studied.

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  • Kidney sections were analyzed using immunofluorescence staining for Ig, HS, heparan sulfate proteoglycan (HSPG)-core protein, and laminin.
  • Agarose electrophoresis and HS inhibition ELISA were used to assess total glomerular HS content.

    • Main Results:

    • Prolonged albuminuria in MRL/lpr mice was associated with a near-complete loss of HS staining in glomerular capillary loops.
    • HS staining was preserved in non-albuminuric mice and showed a trend toward decrease in mice with short albuminuria.
    • No alterations were observed in HSPG-core protein or laminin expression, suggesting specific HS loss.
    • HS staining showed a significant inverse correlation with albuminuria (rs = -0.55) and Ig deposition (rs = -0.74).
    • Despite the loss of staining, total glomerular HS content remained unchanged, indicating masking by Ig deposits.

    Conclusions:

    • The development of albuminuria in lupus nephritis is accompanied by a loss of HS staining in the GBM.
    • This loss of HS staining is likely due to masking by Ig deposits, rather than a reduction in HS quantity.
    • In vitro findings suggest autoantibodies may interfere with HS detection, a mechanism that requires further in vivo validation.