The Parietal Epithelial Cell

Abstract

Abstract. Focal segmental glomerulosclerosis (FSGS) is a hallmark of progressive renal disease. Podocyte injury and loss have been proposed as the critical events that lead to FSGS. In the present study, the authors have examined the development of FSGS in Thy-1.1 transgenic (tg) mice, with emphasis on the podocyte and parietal epithelial cell (PEC). Thy-1.1 tg mice express the Thy-1.1 antigen on podocytes. Injection of antiThy-1.1 mAb induces an acute albuminuria and development of FSGS lesions that resemble human collapsing FSGS. The authors studied FSGS lesions at days 1, 3, 6, 7, 10, 14, and 21, in relation to changes in the expression of specific markers for normal podocytes (WT-1, synaptopodin, ASD33, and the Thy-1.1 antigen), for mouse PEC (CD10), for activated podocytes (desmin), for macrophages (CD68), and for proliferation . The composition of the extracellular matrix (ECM) that forms tuft adhesions or scars was studied using mAb against collagen IV ␣2 and ␣4 chains and antibodies directed against different heparan sulfate species. The first change observed was severe PEC injury at day 1, which increased in time, and resulted in denuded segments of Bowman's capsule at days 6 and 7. Podocytes showed foot process effacement and microvillous transformation. There was no evidence of podocyte loss or denudation of the GBM. Podocytes became hypertrophic at day 3, with decreased expression of ASD33 and synaptopodin and normal expression of WT-1 and Thy-1.1. Podocyte bridges were formed by attachment of hypertrophic podocytes to PEC and podocyte apposition against denuded segments of Bowman's capsule. At day 6, there was a marked proliferation of epithelial cells in Bowman's space. These proliferating cells were negative for desmin and all podocyte markers, but stained for CD10, and thus appeared to be PEC. The staining properties of the early adhesions were identical to that of Bowman's capsule, suggesting that the ECM in the adhesions was produced by PEC. In conclusion, the authors propose the following sequence of events leading to FSGS lesions in the Thy1.1 tg mice: (1) PEC damage and denudation of Bowman's capsule segments; (2) podocyte hypertrophy and bridging; and (3) PEC proliferation with ECM production.

The Regenerative Potential of Parietal Epithelial Cells in Adult Mice

“…This finding is consistent with our previous reports. [17][18][19]27 In the current study, we examined podocyte regeneration under physiologic conditions and in models of glomerular hypertrophy. The choice to use these models was made for several reasons.…”

“…The formation of FSGS lesions and the participation of PECs have already been studied by us previously. [17][18][19] In those studies, we showed, in different Figure 2. Induction of progressive glomerular hypertrophy.…”

Lymphocytes are dispensable for glomerulonephritis but required for renal interstitial fibrosis in matrix defect-induced Alport renal disease

“…The cellular composition of glomerular crescents in the a3KO mouse model does not appear to contain CD3 þ and CD19 þ lymphocytes, but is rather composed of proliferating visceral and parietal glomerular epithelial cells, and possibly macrophages, although their identification in glomerular crescents is challenging. [15][16][17][20][21][22] Overall, deletion of B-cell and T-cells in a3KO mice does not result in a protection from glomerular disease and loss of renal function. Proteinuria remains the same in the a3KO mice and the a3/Rag-1 DKO mice.…”

“…Furthermore, a growing body of evidence has suggested that parietal epithelial cells are involved in crescent formation, with transdifferentiation of parietal epithelial cells and acquisition of new epitopes, shared by macrophages. [15][16][17][18][19][20][21][22][23] These results indicate that origins of glomerulonephritis still remain ambiguous, and mechanisms may differ according to the underlying renal disease.…”

Collapsing Glomerulopathy in 19 Patients with Systemic Lupus Erythematosus or Lupus-Like Disease

“…Humoral factors may play a role in inducing podocyte injury, which was shown in the work by Avila-Casado et al (33); rats injected with serum from patients with CG developed proteinuria, whereas rats injected with FSGS or normal human serum did not. Other mouse models have shown that an antibody-induced glomerular injury produced a CG-like pattern in three different strains of transgenic mice (34)(35)(36). A circulating factor has been postulated to play a role in podocyte injury in FSGS not otherwise specified in the form of high soluble urokinase receptor (37).…”