Glomerular parietal epithelial cells in kidney physiology, pathology, and repair

Abstract

Purpose of reviewWe have summarized recently published glomerular parietal epithelial cell (PEC) research, focusing on their roles in glomerular development and physiology, and in certain glomerular diseases. The rationale is that PECs have been largely ignored until the recent availability of cell lineage tracing studies, human and murine PEC culture systems, and potential therapeutic interventions of PECs. Recent findingsSeveral new paradigms involving PECs have emerged demonstrating their significant contribution to glomerular physiology and numerous glomerular diseases. A subset of PECs serving as podocyte progenitors have been identified in normal human glomeruli. They provide a source for podocytes in adolescent mice, and their numbers increase in states of podocyte depletion. PEC progenitor number is increased by retinoids and angiotensin-converting enzyme inhibition. However, dysregulated growth of PEC progenitors leads to pseudo-crescent and crescent formation. In focal segmental glomerulosclerosis, considered a podocyte disease, activated PECs increase extracellular matrix production, which leads to synechial attachment and, when they move to the glomerular tuft, to segmental glomerulosclerosis. Finally, PECs might be adversely affected in proteinuric states by undergoing apoptosis. SummaryPECs play a critical role in glomerular repair through their progenitor function, but under certain circumstances paradoxically contribute to deterioration by augmenting scarring and crescent formation.

Podocyte Number in Children and Adults

“…53,54 Podocytes can be induced to proliferate in vitro when cultured from freshly isolated glomeruli, 55 but these cells express low levels of many of the podocyte-specific differentiation markers, suggesting that podocytes are only capable of proliferating after they have dedifferentiated to a certain degree. Recent evidence suggests that progenitor cells residing in the JGA 56 and Bowman's capsule (PECs) [57][58][59][60][61] may give rise to podocytes. Other lines of evidence suggest that new podocytes may arise from bone marrow.…”

“…There is much interest in whether PECs can give rise to podocytes. 59,65 Wanner et al 66 recently showed that podocyte generation is mainly active during glomerular development and may occur after acute glomerular injury but was not observed in aging kidneys or in response to nephron loss. Interestingly, a recent study by Berger et al 67 showed that parietal podocytes (PECs expressing podocyte markers) disappeared from Bowman's capsule as glomeruli gradually underwent physiologic hypertrophy, suggesting that there is a functional podocyte reserve that directly differentiates into podocytes on Bowman's capsule.…”

“…57,59,83,84 Activated PECs can avidly proliferate, migrate, and produce extracellular matrix. 85 To our knowledge, this study provides the first estimates of total PEC numbers in human glomeruli.…”

Glomerular parietal epithelial cell activation induces collagen secretion and thickening of Bowman's capsule in diabetes

“…The physiological size of PECs ranges from 0.1-0.3 mm increasing to 2.0-3.5 mm in the perinuclear area. 20 Therefore, morphological features of activation were defined as PECs with an enlarged (43.5 mm) and hyperchromatic nucleus. We performed the measurements of the Bowman's capsule by drawing lines in distances of 10 mm around the whole glomerulus under  1250-1600 original magnification using the image SP viewer (SysProg, Minsk, Belarus; Figure 1).…”

Podocyte directed therapy of nephrotic syndrome—can we bring the inside out?

“…Other mechanisms of recovery involve glomerular cell replacement from stem cells. A glomerular stem cell niche was recently described which implies that lost podocytes could be replaced by cells from the parietal layer [7][8][9]. Whether this concept is only part of a physiological replenishment or holds true in disease states is a controversial discussion since parietal epithelial cells are clearly involved in the disease process itself [10][11][12][13].…”