Abstract
Podocyte depletion plays a major role in focal segmental glomerular sclerosis (FSGS). Because cells of the renin lineage (CoRL) serve as adult podocyte and parietal epithelial cell (PEC) progenitor candidates, we generated Ren1cCre/R26R-ConfettiTG/WT and Ren1dCre/R26R-ConfettiTG/WT mice to determine CoRL clonality during podocyte replacement. Four CoRL reporters (GFP, YFP, RFP, CFP) were restricted to cells in the juxtaglomerular compartment (JGC) at baseline. Following abrupt podocyte depletion in experimental FSGS, all four CoRL reporters were detected in a subset of glomeruli at day 28, where they co-expressed de novo four podocyte proteins (podocin, nephrin, WT-1 and p57) and two glomerular parietal epithelial cell (PEC) proteins (claudin-1, PAX8). To monitor the precise migration of a subset of CoRL over a 2w period following podocyte depletion, intravital multiphoton microscopy was used. Our findings demonstrate direct visual support for the migration of single CoRL from the JGC to the parietal Bowman’s capsule, early proximal tubule, mesangium and glomerular tuft. In summary, these results suggest that following podocyte depletion, multi-clonal CoRL migrate to the glomerulus and replace podocyte and PECs in experimental FSGS.
Highlights
Abrupt podocyte depletion in Ren1cCre/R26R-ConfettiTG/WT mice is followed by partial replacement by another cell type
These results show that these characteristic features of focal segmental glomerular sclerosis (FSGS) are similar in this mouse strain to others [15, 32, 33] with initial podocyte depletion and glomerulosclerosis, followed by partial recovery
In the current study we show that following podocyte injury, cells of the renin lineage (CoRL) populate the glomeruli, and adopt phenotypic characteristics of both glomerular epithelial cell types namely podocytes and parietal epithelial cells (PECs)
Summary
The absence of renin staining in these IGC reporter positive cells (Fig 2E and 2F) suggests that CoRL appear to migrate from the JGC to the IGC (Fig 3B and 3C) On D28 FSGS the percentage of glomeruli with absent reporter colors in intra-glomerular compartment (IGC) decreased significantly compare to baseline (34.67±5.05 vs 96.67±4.16 p
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