Abstract
The coxsackie- and adenovirus receptor (CXADR) is a member of the immunoglobulin protein superfamily, present in various epithelial cells including glomerular epithelial cells. Beside its known function as a virus receptor, it also constitutes an integral part of cell-junctions. Previous studies in the zebrafish pronephros postulated a potential role of CXADR for the terminal differentiation of glomerular podocytes and correct patterning of the elaborated foot process architecture. However, due to early embryonic lethality of constitutive Cxadr knockout mice, mammalian data on kidney epithelial cells have been lacking. Interestingly, Cxadr is robustly expressed during podocyte development and in adulthood in response to glomerular injury. We therefore used a conditional transgenic approach to elucidate the function of Cxadr for podocyte development and stress response. Surprisingly, we could not discern a developmental phenotype in podocyte specific Cxadr knock-out mice. In addition, despite a significant up regulation of CXADR during toxic, genetic and immunologic podocyte injury, we could not detect any impact of Cxadr on these injury models. Thus these data indicate that in contrast to lower vertebrate models, mammalian podocytes have acquired molecular programs to compensate for the loss of Cxadr.
Highlights
The renal filtration barrier is composed of at least four layers, the endothelial glycocalyx, the endothelial fenestrae, the glomerular basement membrane and the slit diaphragm (SD) in between neighbouring podocyte foot processes [1]
Within the kidney Cxadr was localized to glomerular podocytes and epithelial cells of several tubular segments including the proximal tubule and the thick ascending limb of Henle (Fig 1E and 1F +S1 Fig)
The expression of coxsackie- and adenovirus receptor (CXADR) in podocytes vanished by 6 weeks of age, while parietal epithelial cell expression remained constantly high (S1C–S1E Fig)
Summary
The renal filtration barrier is composed of at least four layers, the endothelial glycocalyx, the endothelial fenestrae, the glomerular basement membrane and the slit diaphragm (SD) in between neighbouring podocyte foot processes [1]. This last part of the filter is composed of a variety of different types of intercellular junctions, forming a uniquely broad, permeable and still highly selective barrier. Beside slit-diaphragm specific components such as NEPHRIN, PLOS ONE | DOI:10.1371/journal.pone.0129424. CXADR and Podocyte had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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