Abstract: TH-PO076

Sox-9 Is a Marker for Activated Parietal Epithelial Cells and Potentially Involved in Podocyte Regeneration in a Rat Anti-GBM Nephritis Model

Session Information

Category: Glomerular

  • 1002 Glomerular: Basic/Experimental Pathology

Authors

  • Daniel, Christoph, University Erlangen-Nürnberg, Erlangen, Germany
  • Prochnicki, Ania, FAU Erlangen, Erlangen, Germany
  • Pippin, Jeffrey W., University of Washington, Seattle, Washington, United States
  • Shankland, Stuart J., University of Washington, Seattle, Washington, United States
  • Amann, Kerstin U., FAU Erlangen, Erlangen, Germany
Background

In healthy kidneys parietal epithelial cells (PECs) line out the Bowman’s capsule. During renal disease PECs are thought to be involved in crescent formation as well as in podocyte regeneration. However, the activation of PECs during crescent formation and its potential role in scar formation or podocyte regeneration is not well understood. The aim of the study was to investigate a potential role of the transcription factor Sox9 as a marker of activated PECs in renal development, healthy adult kidneys and during anti-GBM nephritis.

Methods

Renal Sox9 expression was investigated in different species including mouse, rat, pig and humans using immunohistochemistry. Glomerular Sox9 expression was characterized in more detail in healthy (n=11) and anti-glomerular basement membrane (anti-GBM) nephritic (n=11) rats on days 7 and 14 after model induction as well as in newborn rats (n=3) using immunofluorescence double staining and confocal laser scanning microscopy.

Results

In glomeruli from healthy rat kidneys Sox9 expression is restricted to approx. 30% of PECs nuclei. During anti-GBM nephritis the number of glomerular Sox9-positive cells was increased 2-fold on day 7 and about 5-fold on day 14 after disease induction. In nephritic glomeruli Sox9 expression was not restricted to Bowman’s capsule lining but was also found on cells of the glomerular tuft. Nearly all Sox9-positive cells also expressed the parietal epithelial marker Pax8 whereas Ox7-positive mesangial cells, CD31-positive endothelial cells and CD68-positive macrophages lacked Sox9 expression.
While in healthy glomeruli only 4% of Sox9-positive cells showed proliferative activity, during anti-GBM nephritis more than 60% on day 7 and about 40% on day 14 of glomerular Sox9 positive cells also expressed PCNA, a proliferation marker. Of note, on day 7 0.8±0.9 and on day 14 1.6±1.3 cells per glomerular cross-section express both Sox9 and the podocyte marker podocalyxin. In addition, during glomerulogenesis Sox9 was expressed in parietal epithelial cells as well as podocytes.

Conclusion

Our data are in line with Sox9 being a marker of activated parietal epithelial cells and may further point to a potential role in podocyte regeneration.

Funding

  • Government Support - Non-U.S.