Renal Progenitor Cells Contribute to Hyperplastic Lesions of Podocytopathies and Crescentic Glomerulonephritis

Abstract

Glomerular injury can involve excessive proliferation of glomerular epithelial cells, resulting in crescent formation and obliteration of Bowman's space. The origin of these hyperplastic epithelial cells in different glomerular disorders is controversial. Renal progenitors localized to the inner surface of Bowman's capsule can regenerate podocytes, but whether dysregulated proliferation of these progenitors contributes to crescent formation is unknown. In this study, we used confocal microscopy, laser capture microdissection, and real-time quantitative reverse transcriptase-PCR to demonstrate that hypercellular lesions of different podocytopathies and crescentic glomerulonephritis consist of three distinct populations:TGF-␤ induced CD133 ϩ CD24 ϩ progenitors to produce extracellular matrix, and these were the only cells to express the proliferation marker Ki67. Taken together, these results suggest that glomerular hyperplastic lesions derive from the proliferation of renal progenitors at different stages of their differentiation toward mature podocytes, providing an explanation for the pathogenesis of hyperplastic lesions in podocytopathies and crescentic glomerulonephritis.

The Pathogenesis of Lupus Nephritis

“…79 In addition, cellular glomerular crescent formation results from activation of parietal epithelial cells that fill the urinary space by uncoordinated proliferation. 80,81 This process can be triggered by glomerular basement membrane breaks that allow plasma leakage into Bowman's space, where mitogenic plasma components such as fibrinogen trigger hyperproliferation of the parietal epithelial cells. 82 At later stages, the parietal epithelial cells lose their polarity and produce matrix all around themselves, which creates honeycomb matrix deposits in Bowman's space that turn cellular crescents into fibrocellular crescents with glomerulosclerosis, also referred to as class VI LN.…”

Podocyte Mitosis – A Catastrophe

“…First, glomerular progenitors may make the prevention and treatment of glomerulosclerosis possible. However, this regenerative process can also sometimes be inadequate because of an inefficient or, in some situations, excessive, proliferative response [107, 110]. Converging evidence indicates the type of pathologic or clinic presentation, or even the outcome of glomerular disorders, may depend on the balance between injury of podocytes, and the regeneration provided by progenitors.…”

Characterization of Renal Progenitors Committed Toward Tubular Lineage and Their Regenerative Potential in Renal Tubular Injury

“…However, whether these regenerating cells derive from differentiated tubular cells or from a subset of renal stem/progenitor cells localized within the nephron remains unknown. In other adult organs, resident stem cell compartments critically participate in regeneration [5,6], and several studies support the existence of a stem/progenitor cell compartment also in adult mammalian kidney [7][8][9][10][11][12][13][14][15][16][17]. Renal progenitors were first identified in humans, where they are characterized by coexpression of two markers, CD133 and CD24 [7][8][9][10][11][12][13][14].…”

“…In other adult organs, resident stem cell compartments critically participate in regeneration [5,6], and several studies support the existence of a stem/progenitor cell compartment also in adult mammalian kidney [7][8][9][10][11][12][13][14][15][16][17]. Renal progenitors were first identified in humans, where they are characterized by coexpression of two markers, CD133 and CD24 [7][8][9][10][11][12][13][14]. CD133þCD24þ human renal progenitors are localized at the urinary pole of Bowman's capsule [7][8][9][10][11][12][13][14] and are capable of podocyte and tubular differentiation [7][8][9][10]17].…”

“…Renal progenitors were first identified in humans, where they are characterized by coexpression of two markers, CD133 and CD24 [7][8][9][10][11][12][13][14]. CD133þCD24þ human renal progenitors are localized at the urinary pole of Bowman's capsule [7][8][9][10][11][12][13][14] and are capable of podocyte and tubular differentiation [7][8][9][10]17]. However, the tubular portion of the nephron is very long, which suggests that the stem cell compartment localized at the urinary pole of Bowman's capsule may not be unique and that other progenitors may localize along the tubular part of the M.L.A., E.R., L.B., B.M., A.P., C.S., E.P., M.R., and E.L.: collection and/or assembly of data, data analysis and interpretation, and final approval of manuscript; M.G.…”