Abstract
In normal glomeruli, parietal epithelial cells (PECs) line the inside of Bowman’s capsule and form an inconspicuous sheet of flat epithelial cells in continuity with the proximal tubular epithelial cells (PTECs) at the urinary pole and with the podocytes at the vascular pole. PECs, PTECs and podocytes have a common mesenchymal origin and are the result of divergent differentiation during embryogenesis. Podocytes and PTECs are highly differentiated cells with well-established functions pertaining to the maintenance of the filtration barrier and transport, respectively. For PECs, no specific function other than a structural one has been known until recently. Possible important functions for PECs in the fate of the glomerulus in glomerular disease have now become apparent: (1) PECs may be involved in the replacement of lost podocytes; (2) PECs form the basis of extracapillary proliferative lesions and subsequent sclerosis in glomerular disease. In addition to the acknowledgement that PECs are crucial in glomerular disease, knowledge has been gained regarding the molecular processes driving the phenotypic changes and behavior of PECs. Understanding these molecular processes is important for the development of specific therapeutic approaches aimed at either stimulation of the regenerative function of PECs or inhibition of the pro-sclerotic action of PECs. In this review, we discuss recent advances pertaining to the role of PECs in glomerular regeneration and disease and address the major molecular processes involved.
Highlights
Podocyte regeneration by parietal epithelial cellsPodocytes play a key role in maintaining the glomerular filtration barrier and podocyte dysfunction or podocyte loss is the determining factor for the initiation and progression of glomerulosclerosis (Kriz et al 1998)
In normal glomeruli, parietal epithelial cells (PECs) line the inside of Bowman’s capsule and form an inconspicuous sheet of flat epithelial cells in continuity with the proximal tubular epithelial cells (PTECs) at the urinary pole and with the podocytes at the vascular pole
Podocytes play a key role in maintaining the glomerular filtration barrier and podocyte dysfunction or podocyte loss is the determining factor for the initiation and progression of glomerulosclerosis (Kriz et al 1998)
Summary
Podocytes play a key role in maintaining the glomerular filtration barrier and podocyte dysfunction or podocyte loss is the determining factor for the initiation and progression of glomerulosclerosis (Kriz et al 1998). Several studies have argued in favor of podocyte replacement by PECs based on the finding of the increased co-expression of podocyte- and PEC-specific markers, either on cells lining Bowman’s capsule or on the glomerular tuft. Lasagni et al (2015) demonstrated that, in animals that have attained disease remission after the previous induction of acute podocyte injury, podocytes are regenerated from PECs. Later, a suppopulation of the traced PECs expresses podocyte markers without Erk-1 (Eng et al 2015). Lasagni et al (2015) demonstrated that, in animals that have attained disease remission after the previous induction of acute podocyte injury, podocytes are regenerated from PECs In these animals, the genetic PEC reporter signal has been traced in cells that, based on their location, phenotype and marker expression, resemble podocytes (Lasagni et al 2015). Difficulties will be experienced in establishing podocyte regeneration, as this would require the accurate assessment of podocyte numbers in successive renal biopsies and would require information concerning podocyte loss
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