Podocytes Contribute to the Formation of Glomerular Crescents

Abstract

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. Keratinpositive 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.

Origin of Parietal Podocytes in Atubular Glomeruli Mapped by Lineage Tracing

“…Thus far, podocytes have only been proven to migrate onto Bowman's capsule in the context of an acute inflammatory nephritis such as rapidly progressive GN (RPGN). 31,[45][46][47] In RPGN, podocytes dedifferentiate and migrate via direct adhesions onto Bowman's capsule. There they contribute to the formation of cellular crescents by proliferation together with activated PECs.…”

Aspectos histopatológicos das lesões renais em gatos experimentalmente infectados pelo vírus da imunodeficiência felina

“…Entretanto, ainda há controvérsias a respeito da origem das células hiperplásicas no interior dos glomérulos (Bruggeman & Nelson 2009). Alguns estudos, nos quais marcadores celulares foram utilizados, sugerem que as cé-lulas presentes nas pseudocrescentes na HIVAN e em outras glomerulopatias colapsantes se originem das células epiteliais parietais e não dos podócitos (Nagata et al 1998, Dijkman et al 2006, ao passo que os podócitos também podem contribuir, de certa maneira, para a formação das crescentes glomerulares (Thorner et al 2008, Sistani et al 2012. Os resultados conflitantes caracterizados pela detecção de alguns marcadores específicos de podócitos nas crescentes glomerulares e não detecção de outros poderia ser explicado pela diferenciação dos podócitos e perda de alguns marcadores específicos com a progressão da doença (Sistani et al 2012).…”

Adult Stem Cells in Tissue Homeostasis and Disease

“…In the glomerulus, the response to podocyte injury may cause aberrant epithelial cell proliferation, hypercellular lesions formation and Bowman's space obliteration, as seen in collapsing glomerulopathy and in crescentic glomerulonephritis (Albaqumi & Barisoni, 2008;Thorner, et al, 2008). Until now, theories explaining the origin of aberrant epithelial cells in collapsing glomerulopathy and crescentic glomerulonephritis have been controversial.…”

“…Until now, theories explaining the origin of aberrant epithelial cells in collapsing glomerulopathy and crescentic glomerulonephritis have been controversial. One possibility is that these cells are exclusively of parietal epithelial origin (Thorner et al, 2008 ), while another is that some dedifferentiated podocytes acquire markers of parietal epithelial cells (Moeller et al, 2004). It was recently demonstrated that the majority of cells present in the hyperplastic lesions in collapsing glomerulopathy or crescentic glomerulonephritis exhibits the RSC markers CD133 and CD24, with or without coexpression of podocyte markers .…”