PARIETAL EPITHELIAL CELLS

Biology of glomerular parietal epithelial cells (PECs):

The study and understanding of PECs has lacked significantly compared to other kidney cells, such that their functions and roles in the pathobiology of glomerular diseases

have only been delineated in the past 5+ years, and as a community, we likely have only scratched the surface. We have made several important contributions to the field to

date.

 

1)  we showed that by expressing several tight junction proteins, PECs serve an important role in limiting the passage of protein from the urinary space to the

extraglomerular space (a). Indeed, when tight junctions are disrupted in disease, albumin and other proteins escape into the extra- glomerular space, where they

contribute to the peri-glomerular inflammation and fibrosis that characterized progressive proteinuric glomerular diseases. 

 

(a) Ohse T, Chang AM, Pippin JW, Jarad G, Hudkins KL, Alpers CE, Miner JH, Shankland SJ. A     new function for parietal epithelial cells: a second glomerular barrier. Am

J Physiol Renal. 2009;297(6):F1566-74. PMID 19794110. PMCID: 2801333.

 

2)  we developed the first immortalized mouse PEC line for study in cell culture (b). These cells are now widely used by numerous groups internationally, from which

many publications have arisen.

 

(b) Ohse T, Pippin JW, Vaughan MR, Brinkkoetter PT, Shankland SJ. Establishment of conditionally     immortalized mouse glomerular parietal epithelial cells in culture.

J Am Soc Nephrol. 2008;19(10):1879-90. PMID: 18596122. PMCID: 2551564

 

3)  we have several publications showing that the expression profile, and likely biological functions of PECs, changes in settings where podocytes are the primary target

of disease (c1). Our data shows that in states of podocyte depletion, PECs lining Bowman’s capsule begin to co-express several proteins considered specific for

podocytes. A subset of PECs co-expressing podocyte proteins migrate to the glomerular tuft, suggesting that they may serve as adult podocyte progenitors. We have

also published three additional manuscripts showing that when mice are given either dexamethasone, ACE-inhibitors or retinoids, that the improvement in podocyte

number coincides with an increase in the subset of PECs expressing podocyte proteins. These studies strongly suggest an adult podocyte progenitor function for PECs

in states of podocyte depletion. In a mouse model of focal segmental glomerulosclerosis typified by abrupt podocyte depletion followed by regeneration, PECs can

participate in either a pro-fibrotic or regenerative pathway once they migrate to the glomerular tuft. An initial pro-fibrotic response is predominated by activated PECs

that are CD44+ and phospho-ERK+, while a later regenerative response is typified by CD44+ phosphor-ERK- progenitor cells that co-express podocyte proteins (c2).

 

(c1) Zhang J, Pippin JW, Krofft RD, Naito S, Liu ZH, Shankland SJ. Podocyte repopulation by renal progenitor cells following glucocorticoids treatment in experimental

FSGS. Am J Physiol Renal2013;304(11):F1375-89. PMID: 23486009. PMCID: 3680690.

 

(c2) Eng DG, Sunseri MW, Kaverina NV, Roeder SS, Pippin JW, Shankland SJ. Glomerular parietal epithelial cells contribute to adult podocyte regeneration in

experimental focal segmental glomerulosclerosis. Kidney Int. 2015 Nov;88(5):999-1012. PMID: 25993321. PMCID: 4654724.

 

4)  the exact genetic makeup of PECs is not known, and the field needs to better understand what genes are constitutively expressed by PECs. We have reported on the

transcriptional landscape for PECs, and how this profile differs from neighboring podocytes (d). These studies have already benefited the community, as many are using

this dataset for further studies.

 

(d) Gharib SA, Pippin JW, Ohse T, Pickering SG, Krofft RD, Shankland SJ. Transcriptional     landscape of glomerular parietal epithelial cells. PLoS One. 2014 Aug 15;9(8)

PMID: 25127402.  PMCID: 4134297.