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 viscer...

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Bibliographic Details
Published in:Journal of the American Society of Nephrology 2004-01, Vol.15 (1), p.61-67
Main Authors: Moeller, Marcus J, Soofi, Abdulsalaam, Hartmann, Inge, Le Hir, Michel, Wiggins, Roger, Kriz, Wilhelm, Holzman, Lawrence B
Format: Article
Language:English
Subjects:
Animals
Disease Models, Animal
Epithelial Cells
Glomerulonephritis - pathology
Kidney Glomerulus - cytology
Mice
Mice, Inbred C57BL
Urothelium - cytology
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Summary: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.
ISSN:1046-6673
DOI:10.1097/01.ASN.0000102468.37809.C6