Podocytes populate cellular crescents in a murine model of inflammatory glomerulonephritis.
Cellular crescents are a defining histologic finding in many forms of inflammatory glomerulonephritis. Despite numerous studies, the origin of glomerular crescents remains unresolved. A genetic cell lineage-mapping study with a novel transgenic mouse model was performed to investigate whether visceral glomerular epithelial cells, termed podocytes, are precursors of cells that populate cellular crescents. The podocyte-specific 2.5P-Cre mouse line was crossed with the ROSA26 reporter line, resulting in irreversible constitutive expression of beta-galactosidase in doubly transgenic 2.5P-Cre/ROSA26 mice. In these mice, crescentic glomerulonephritis was induced with a previously described rabbit anti-glomerular basement membrane antiserum nephritis approach. Interestingly, beta-galactosidase-positive cells derived from podocytes adhered to the parietal basement membrane and populated glomerular crescents during the early phases of cellular crescent formation, accounting for at least one-fourth of the total cell mass. In cellular crescents, the proliferation marker Ki-67 was expressed in beta-galactosidase-positive and beta-galactosidase-negative cells, indicating that both cell types contributed to the formation of cellular crescents through proliferation in situ. Podocyte-specific antigens, including WT-1, synaptopodin, nephrin, and podocin, were not expressed by any cells in glomerular crescents, suggesting that podocytes underwent profound phenotypic changes in this nephritis model.
Moeller
Marcus J
MJ
Division of Nephrology, Department of Internal Medicine, University of Michigan, and Department of Veterans Affairs, Ann Arbor, Michigan, USA. marcus.moeller@urz.uni-heidelberg.de
Soofi
Abdulsalaam
A
Hartmann
Inge
I
Le Hir
Michel
M
Wiggins
Roger
R
Kriz
Wilhelm
W
Holzman
Lawrence B
LB
D000818:Animals; D004195:Disease Models, Animal; D004847:Epithelial Cells; D005921:Glomerulonephritis / Q000473:pathology*; D007678:Kidney Glomerulus / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D019459:Urothelium / Q000166:cytology