Tracing the origin of glomerular extracapillary lesions from parietal epithelial cells.
Cellular lesions form in Bowman's space in both crescentic glomerulonephritis and collapsing glomerulopathy. The pathomechanism and origin of the proliferating cells in these lesions are unknown. In this study, we examined proliferating cells by lineage tracing of either podocytes or parietal epithelial cells (PECs) in the nephrotoxic nephritis model of inflammatory crescentic glomerulonephritis. In addition, we traced the fate of genetically labeled PECs in the Thy-1.1 transgenic mouse model of collapsing glomerulopathy. In both models, cellular bridges composed of PECs were observed between Bowman's capsule and the glomerular tuft. Genetically labeled PECs also populated larger, more advanced cellular lesions. In these lesions, we detected de novo expression of CD44 in activated PECs. In contrast, we rarely identified genetically labeled podocytes within the cellular lesions of crescentic glomerulonephritis. In conclusion, PECs constitute the majority of cells that compose early extracapillary proliferative lesions in both crescentic glomerulonephritis and collapsing glomerulopathy, suggesting similar pathomechanisms in both diseases.
Smeets
Bart
B
Department of Nephrology and Immunology, University Hospital of the Aachen University of Technology, Pauwelsstrasse 30, Aachen, Germany. b.smeets@pathol.umcn.nl
Uhlig
Sandra
S
Fuss
Astrid
A
Mooren
Fieke
F
Wetzels
Jack F M
JF
Floege
Jürgen
J
Moeller
Marcus J
MJ
D000818:Animals; D050476:Bowman Capsule / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D062445:Claudin-1; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005921:Glomerulonephritis / Q000378:metabolism / Q000473:pathology*; D018960:Hyaluronan Receptors / Q000378:metabolism; D006965:Hyperplasia; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D050199:Podocytes / Q000378:metabolism / Q000473:pathology
C476399:Cd44 protein, mouse; D062445:Claudin-1; C568113:Cldn1 protein, mouse; D018960:Hyaluronan Receptors; D008565:Membrane Proteins