Podocyte-Parietal Epithelial Cell Interdependence in Glomerular Development and Disease

Abstract

Podocytes and parietal epithelial cells (PECs) are among the few principal cell types within the kidney glomerulus, the former serving as a crucial constituent of the kidney filtration barrier and the latter representing a supporting epithelial layer that adorns the inner wall of Bowman's capsule. Podocytes and PECs share a circumscript developmental lineage that only begins to diverge during the S-shaped body stage of nephron formation–occurring immediately before the emergence of the fully mature nephron. These two cell types, therefore, share a highly conserved gene expression program, evidenced by recently discovered intermediate cell types occupying a distinct spatiotemporal gene expression zone between podocytes and PECs. In addition to their homeostatic functions, podocytes and PECs also have roles in kidney pathogenesis. Rapid podocyte loss in diseases, such as rapidly progressive GN and collapsing and cellular subtypes of FSGS, is closely allied with PEC proliferation and migration toward the capillary tuft, resulting in the formation of crescents and pseudocrescents. PECs are thought to contribute to disease progression and severity, and the interdependence between these two cell types during development and in various manifestations of kidney pathology is the primary focus of this review.

Membranous nephropathy: pathogenesis and treatments

“…Attached to the outer layer of the GBM, 64 the peduncle is pivotal in the renal filtration barrier, engaging with intercellular junctions and matrix proteins. 65 , 66 Notably, the apical domains of the peduncle bear a negative charge, facilitating the retention of negatively charged molecules like albumin and preserving the integrity of neighboring peduncles through anionic charge separation. 67 As a special epithelial cell of the glomerulus, podocytes surround the glomerular capillary wall and have special shapes, structures and functions.…”

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

“…While the different categories of glomerulopathies are causally associated with heterogeneous stimuli and diverse pathogenetic routes, they converge towards a common feature, which is the impairment of podocytes structural and/or functional integrity. A compensatory mechanism activated by the kidney in order to cope with podocyte injury and the impeding of the glomerular filtration barrier is the mobilization of parietal epithelial cells (PECs), which share common developmental ancestries and evince a close lineage relationship with podocytes [7][8][9][10][11]. 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.…”

“…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].…”

“…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]. Moreover, it seems that as an adaptive response to specific pathogenic triggers imposed upon podocytes, PECs can also re-enter the cell cycle and form cellular masses that occupy the Bowman capsule, as observed in the collapsing variant of FSGS, or crescentic glomerulonephritis [7][8][9][10][11]. In such cases, they maintain their PEC identity without acquiring features or expressing markers indicative of podocytic differentiation.…”

Ursolic Acid Alleviates Mitotic Catastrophe in Podocyte by Inhibiting Autophagic P62 Accumulation in Diabetic Nephropathy

“…The glomerular podocyte, a highly differentiated specialized visceral cell, is located on the outer surface of the glomerular basement membrane (GBM) and, together with the perforated endothelial cell, constitutes the glomerular filtration barrier (GFB). Injured podocytes undergo foot process effacement and detachment, exposing denuded areas on the glomerular capillaries, which results in proteinuria 5 . Moreover, the loss of podocytes, whether through death or detachment, precedes the increased volume of glomeruli, providing strong evidence for early-stage DN diagnosis 6 .…”