Metalloprotease meprin beta in rat kidney: glomerular localization and differential expression in glomerulonephritis

Beatrice Oneda1, Nadège Lods, Daniel Lottaz

  • 1Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland.

Plos One
|May 30, 2008
PubMed

Insights

Meprin beta, a kidney enzyme, is newly found in rat glomerular cells and podocyte foot processes. Its expression changes in experimental kidney diseases, suggesting a role in glomerular injury.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Enzymology

Background:

  • Meprin (EC 3.4.24.18) is an oligomeric metalloendopeptidase typically located in the microvillar membranes of kidney proximal tubular epithelial cells.
  • Its presence and function in glomerular epithelial cells, particularly podocytes, remain largely uncharacterized.

Purpose of the Study:

  • To investigate the expression and localization of meprin beta in rat glomerular epithelial cells.
  • To explore the potential involvement of meprin beta in the pathogenesis of experimental glomerular diseases, specifically anti-Thy 1.1 glomerulonephritis and passive Heymann nephritis (PHN).

Main Methods:

  • Immunohistochemistry and immuno-gold staining on rat kidney sections to detect meprin beta protein.
  • Quantitative reverse transcription-polymerase chain reaction (RT-PCR) on laser-capture microdissected glomeruli for mRNA analysis.
  • Western blot and immunoprecipitation assays to assess antigenicity.

Main Results:

  • Meprin beta was detected in rat glomeruli at both protein and mRNA levels, primarily localized to podocyte foot processes.
  • Glomerular meprin beta expression patterns were significantly altered in both anti-Thy 1.1 glomerulonephritis and passive Heymann nephritis models.
  • Meprin beta was recognized by Fx1A antiserum, indicating it may be an auto-antigen in PHN.
  • In anti-Thy 1.1 glomerulonephritis, meprin beta redistributed within tubular epithelial cells.

Conclusions:

  • Meprin beta is expressed in rat glomerular epithelial cells, particularly podocytes, and its expression is modulated during experimental glomerular injury.
  • These findings suggest a potential role for meprin beta in the development or progression of glomerular diseases.
  • Meprin beta may act as an auto-antigen in passive Heymann nephritis and is redistributed in tubular cells during anti-Thy 1.1 glomerulonephritis, highlighting its dynamic involvement in kidney pathology.

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