Abstract
Very little is known about the function of glomerular parietal epithelial cells (PECs). In this study, we performed genome-wide expression analysis on PEC-enriched capsulated vs. PEC-deprived decapsulated rat glomeruli to determine the transcriptional state of PECs under normal conditions. We identified hundreds of differentially expressed genes that mapped to distinct biologic modules including development, tight junction, ion transport, and metabolic processes. Since developmental programs were highly enriched in PECs, we characterized several of their candidate members at the protein level. Collectively, our findings confirm that PECs are multifaceted cells and help define their diverse functional repertoire.
Highlights
Parietal epithelial cells (PECs) are epithelial cells in the glomerulus that form a monolayer on the urinary side of Bowman’s capsule [1]. Endothelial cells, and their immediate neighbors podocytes, PECs have not been extensively studied. This mysterious cell has attracted significant interest as some of its functions have been unraveled under physiological states [2,3] For example, the tight junction proteins Claudin-1 and -2 have been identified in PECs that likely function as a secondary barrier to urinary filtrate [4]
Twelve differentially upregulated genes (.2-fold, adjusted P-value,0.01) in PEC-enriched samples were selected for confirmation in murine PECs (mPECs): Aldh1a1, Cdh6, Hnf1b, Lad1, Wwc1, Clmn, Cdh11, Cdkl1, Fras1 (Fraser syndrome 1), Tfcp2l1, Prelp, and
In this work we developed a novel and practical method to isolate PEC-enriched cells from rat glomeruli in vivo, and applied transcriptional profiling to systematically delineate potential biologic functions attributable to these cells under normal conditions
Summary
Parietal epithelial cells (PECs) are epithelial cells in the glomerulus that form a monolayer on the urinary side of Bowman’s capsule [1]. Endothelial cells, and their immediate neighbors podocytes, PECs have not been extensively studied This mysterious cell has attracted significant interest as some of its functions have been unraveled under physiological states [2,3] For example, the tight junction proteins Claudin-1 and -2 have been identified in PECs that likely function as a secondary barrier to urinary filtrate [4]. PECs have been shown to likely serve as resident kidney stem cells in humans [5,6,7,8] as precursors for adult podocytes [9], and as transitional cells that express proteins of both PEC and podocyte origin in experimental disease states [10,11] While these studies have advanced our understanding of the important role played by PECs in health and disease, many properties of these cells remain undiscovered. We postulated that performing a comprehensive and unbiased assessment of PEC gene expression under normal, uninjured condition would shed light on its functional diversity and identify putative candidates mediating these biologic roles
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