TY - JOUR
T1 - Podocytes contribute to the formation of glomerular crescents
AU - Thorner, Paul Scott
AU - Ho, Michael
AU - Eremina, Vera
AU - Sado, Yoshikazu
AU - Quaggin, Susan
PY - 2008/3
Y1 - 2008/3
N2 - The cellular composition of crescents in glomerular disease is controversial. The role of podocytes in crescent formation has been especially difficult to study because podocytes typically lose their characteristic terminally differentiated phenotype under disease conditions, making them difficult to identify. We reasoned that the intermediate filament protein nestin, a marker of progenitor cells that has recently been identified in podocytes, may allow the investigation of podocyte involvement in glomerular crescents. In a series of 35 biopsies with crescentic glomerular disease, all showed nestin-positive cells in the crescents, ranging in number from occasional to approximately 50% of crescent cells. Other podocyte markers, such as podocin and WT1, failed to identify cells in crescents, and no contribution by endothelial or myogenic cells was noted. CD68-positive cells were observed in 80% of cases but were never as numerous as the nestin-positive cells. Nestin and CD68 were not coexpressed by the same cells, providing no evidence of trans-differentiation of podocytes into a macrophage phenotype. Keratin-positive cells were found in crescents in 51% of cases, but only as occasional cells. Up to one third of crescent cells were cycling in 48% of biopsies, and double immunostaining identified these cells as a mixture of nestin-positive cells and "null" cells (negative for nestin, CD68, and keratin). In addition to our observations in human disease, we also identified nestin-positive proliferating podocytes in the crescents of 2 mouse models of crescentic glomerulonephritis. We conclude that podocytes play a role in the formation of glomerular crescents.
AB - The cellular composition of crescents in glomerular disease is controversial. The role of podocytes in crescent formation has been especially difficult to study because podocytes typically lose their characteristic terminally differentiated phenotype under disease conditions, making them difficult to identify. We reasoned that the intermediate filament protein nestin, a marker of progenitor cells that has recently been identified in podocytes, may allow the investigation of podocyte involvement in glomerular crescents. In a series of 35 biopsies with crescentic glomerular disease, all showed nestin-positive cells in the crescents, ranging in number from occasional to approximately 50% of crescent cells. Other podocyte markers, such as podocin and WT1, failed to identify cells in crescents, and no contribution by endothelial or myogenic cells was noted. CD68-positive cells were observed in 80% of cases but were never as numerous as the nestin-positive cells. Nestin and CD68 were not coexpressed by the same cells, providing no evidence of trans-differentiation of podocytes into a macrophage phenotype. Keratin-positive cells were found in crescents in 51% of cases, but only as occasional cells. Up to one third of crescent cells were cycling in 48% of biopsies, and double immunostaining identified these cells as a mixture of nestin-positive cells and "null" cells (negative for nestin, CD68, and keratin). In addition to our observations in human disease, we also identified nestin-positive proliferating podocytes in the crescents of 2 mouse models of crescentic glomerulonephritis. We conclude that podocytes play a role in the formation of glomerular crescents.
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U2 - 10.1681/ASN.2006101115
DO - 10.1681/ASN.2006101115
M3 - Article
C2 - 18199804
AN - SCOPUS:40449083921
SN - 1046-6673
VL - 19
SP - 495
EP - 502
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 3
ER -