Characterization of Glomerular Sox9+ Cells in Anti-Glomerular Basement Membrane Nephritis in the Rat

Abstract

Mechanisms of glomerular crescent formation and podocyte repair processes are still unclear. Therefore, we investigated the expression of the transcription factor Sox9 as a potential marker of a subpopulation of parietal epithelial cells (PECs) with potential regenerative properties. Glomerular Sox9 expression was characterized in detail in a rat anti-glomerular basement membrane (GBM) nephritis model using immunofluorescence and confocal laser scanning microscopy. In healthy kidneys Sox9 is expressed in a subpopulation of PECs restricted to approximately 20% to 50% of PEC nuclei and was highly conserved in all investigated species. During rat anti-GBM nephritis the number of glomerular Sox9+ cells increased and was associated with proliferation activity. 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+ cells also expressed the PEC marker Pax8, whereas endothelial cells, mesangial cells, macrophages, and T lymphocytes lacked Sox9 expression. At the margins of crescents Sox9+/Pax8+ cells additionally expressed podocyte markers. In contrast, in sclerotic lesions a minority of Sox9+/Pax8+ cells expressed the myofibroblast marker α-smooth muscle actin. In glomerular Sox9+ cells Jagged 1 was up-regulated. During anti-GBM nephritis Sox9+ PECs proliferate and migrate onto the glomerular tuft. Future studies are needed to confirm the origin of Sox9+ cells from PECs and differentiation in both podocytes and/or myofibroblasts.