Novel parietal epithelial cell subpopulations contribute to focal segmental glomerulosclerosis and glomerular tip lesions

Prolonged podocyte depletion in larval zebrafish resembles mammalian focal and segmental glomerulosclerosis

“…14 In our model, PECs proliferated and changed their morphology towards a cuboidal, microvillous phenotype. Taken together, these findings support the hypothesis that upon podocytedepletion, flat PECs transform to cuboidal PECs, as it has recently been shown by Kuppe et al 3 Together with the typical cytomorphology and the expression of pax2a and not podocin, we characterized them as cuboidal PECs that covered the denuded areas of the GBM in the most severely injured 36% of MTZ-treated larvae, which fits previous findings in a murine model of collapsing FSGS. 15 In contrast to that, other groups have suggested, that PECs are recruited to the glomerular tuft and replace podocytes.…”

“…2 Recently, Kuppe et al showed that upon activation, PECs develop a cuboidal phenotype and are more prone to contribute to sclerotic lesions. 3 Since experimental procedures in rodents are not ideally suitable for high-throughput drug screening assays, we and others used the larval zebrafish pronephros as a vertebrate model 4 to study glomerular morphology 5 and permselectivity of the glomerular filtration barrier. 6 At 48 hours past fertilization, zebrafish develop a single glomerulus attached to a pair of tubules.…”

Recognizing diversity in parietal epithelial cells

“…Mice deficient in CD44 have reduced capacity for PEC proliferation in models of both crescentic glomerulonephritis and FSGS. 3 In this issue, Kuppe et al 4 now turn their attention to the previously underrecognized third region of Bowman's capsule-the peritubular region. Here cuboidal cells labeling as PECs (cPECs) share morphological features with proximal tubular cells.…”

“…Proximal tubular extension onto Bowman's capsule in humans is more frequent in men (w15% of glomeruli) than women (w8% of glomeruli) and in the elderly. 4 Regardless of whether cPECs colonize Bowman's capsule, iPECs are always present at the transition between flat PECs and cPECs or between flat PECs and proximal tubular cells. In nontubularized glomeruli, this transition occurs at the tubular neck.…”

The authors reply

“…The authors reply: We thank Dr. Howie 1 for pointing out 2 important characteristics of intermediate parietal epithelial cells (iPECs), which further support our findings. 2 First, his early studies identified mucin-1 (MUC1) expression in human iPECs as an additional marker of the glomerulotubular junction. MUC1 was also expressed de novo on injured proximal tubule cells.…”