Lessons from studies on focal segmental glomerulosclerosis: an important role for parietal epithelial cells?

Abstract

Glomerular diseases are caused by multiple mechanisms. Progressive glomerular injury is characterized by the development of segmental or global glomerulosclerosis independent of the nature of the underlying renal disease. Most studies on glomerular disease focus on the constituents of the filtration barrier (podocytes, glomerular basement membrane (GBM), endothelial cells) or the mesangial cells. Little attention is given to the epithelial cells lining Bowman's capsule, the so called parietal epithelial cells (PECs). This 'lack of attention' is partly explained by the presumed 'passive' function of PECs, which are large, flattened cells that cover Bowman's capsule in a single cell layer and form a barrier between the ultrafiltrate and the periglomerular interstitium, in normal glomerular physiology. A more important reason has been the lack of an established primary role for the parietal epithelium in glomerular diseases. However, in recent years, several studies have demonstrated that PECs are involved in extracapillary proliferation. In addition, PECs can become highly active, proliferating cells, expressing many growth factors, chemokines, cytokines, and their receptors. It was recently demonstrated that PECs also play a part in the development of focal segmental glomerulosclerosis (FSGS). This review summarises current knowledge of the PEC, with emphasis on the role of PECs in the development of FSGS.

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

“…5,[31][32][33][34][35][36][37][38][39][40][41][42][43] One possibility is that these cells are exclusively of parietal epithelial origin, 34,38,40,42 whereas others suggested that some dedifferentiated podocytes acquire markers of PECs 5,31,32,35,36,39,41 ; however, more recent studies demonstrated that the intermediate filament protein nestin, which is specifically expressed during any stage of podocyte development and in the mature cell, may allow the investigation of podocyte involvement in glomerular disorders. 23,43 In this study, we hypothesized that hyperplastic epithelial cells of human glomerulopathies might derive from the two distinct populations of CD133 …”

Regeneration of Glomerular Podocytes by Human Renal Progenitors

“…4 In addition, the results of this study provide an intriguing explanation for the genesis of crescents and pseudocrescents, which are known to reflect uncontrolled proliferation of parietal epithelial cells in response to injury. 30,31 Indeed, it is tempting to speculate that CD133ϩCD24ϩ renal progenitors proliferate in an attempt to replace injured podocytes, but if regeneration occurs in a dysregulated manner it can generate hyperplastic lesions that can lead to renal progenitor depletion, scar formation, and nephron loss.…”

Glomerular Epithelial Stem Cells

“…59 -69 One possibility is these cells are exclusively of parietal epithelial origin, 59 -64 whereas others suggest some dedifferentiated podocytes acquire markers of parietal epithelial cells. [65][66][67][68][69] After the identification of a population of glomerular epithelial stem cells along Bowman's capsule that generate new podocytes, we have explored the possibility that hyperplastic epithelial cells in crescentic glomerulonephritis or collapsing glomerulopathy might result from an aberrant proliferative response of these stem cells. This would easily explain the presence in these lesions of cells with an intermediate phenotype between parietal epithelial cells and podocytes.…”