The Role of Parietal Epithelial Cells in the Pathogenesis of Podocytopathy

Abstract

Podocytopathy is the most common feature of glomerular disorder characterized by podocyte injury- or dysfunction-induced excessive proteinuria, which ultimately develops into glomerulosclerosis and results in persistent loss of renal function. Due to the lack of self-renewal ability of podocytes, mild podocyte depletion triggers replacement and repair processes mostly driven by stem cells or resident parietal epithelial cells (PECs). In contrast, when podocyte recovery fails, activated PECs contribute to the establishment of glomerular lesions. Increasing evidence suggests that PECs, more than just bystanders, have a crucial role in various podocytopathies, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, diabetic nephropathy, IgA nephropathy, and lupus podocytopathy. In this review, we attempt to dissect the diverse role of PECs in the pathogenesis of podocytopathy based on currently available information.

Transcriptional regulation by the NSL complex enables diversification of IFT functions in ciliated versus nonciliated cells

“…S4C). Podoplanin had previously been shown to be a cell surface marker useful for sorting of podocytes, while Prominin1 has previously been demonstrated to mark the parietal epithelial and tubular cells ( 57 , 60 – 64 ). Podoplanin + Prominin1 − cells showed >10-fold higher expression of Wt1, the master transcription factor of podocytes, than Podoplanin + Prominin1 + cells (fig.…”

Modeling Podocyte Ontogeny and Podocytopathies with the Zebrafish

“…The term “podocytopathy” is used to refer to diseases that are believed to initiate with podocyte damage or dysfunction [ 204 , 205 , 206 ]. Given the conservation of human and zebrafish podocytes, zebrafish have been used to model a number of podocytopathies.…”

Keratin Expression in Podocytopathies, ANCA-Associated Vasculitis and IgA Nephropathy

“…PECs make up the inconspicuous inside lining of the Bowman capsule, being in continuity with the podocytes at the vascular pole and the tubular epithelial cells at the tubular pole of the glomeruli. They also seem to be equipped with fate plasticity, as they have demonstrated a context-dependent capacity to serve as renal progenitors, capable of regenerating podocytes [7,12]. The process of their trans-differentiation towards a different cellular identity seems to be step-wise, proceeding via intermediate states of a phenotypic continuum, characterized by a synchronous expression of both podocytic and PEC markers [13,14].…”