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Am J Physiol Renal Physiol. 2015 Jul 15;309(2):F164-78. doi: 10.1152/ajprenal.00144.2015. Epub 2015 May 27.

Changes in glomerular parietal epithelial cells in mouse kidneys with advanced age.

Author information

1
Division of Nephrology, University of Washington, Seattle, Washington; Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
2
Division of Nephrology, University of Washington, Seattle, Washington;
3
Department of Pathology, University of Washington, Seattle, Washington;
4
Department of Nephropathology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany; and.
5
Division of Nephrology, University of Washington, Seattle, Washington; stuartjs@uw.edu.

Abstract

Kidney aging is accompanied by characteristic changes in the glomerulus, but little is known about the effect of aging on glomerular parietal epithelial cells (PECs), nor if the characteristic glomerular changes in humans and rats also occur in very old mice. Accordingly, a descriptive analysis was undertaken in 27-mo-old C57B6 mice, considered advanced age. PEC density was significantly lower in older mice compared with young mice (aged 3 mo), and the decrease was more pronounced in juxtamedullary glomeruli compared with outer cortical glomeruli. In addition to segmental and global glomerulosclerosis in older mice, staining for matrix proteins collagen type IV and heparan sulfate proteoglycan were markedly increased in Bowman's capsules of older mouse glomeruli, consistent with increased extracellular matrix production by PECs. De novo staining for CD44, a marker of activated and profibrotic PECs, was significantly increased in aged glomeruli. CD44 staining was more pronounced in the juxtamedullary region and colocalized with phosphorylated ERK. Additionally, a subset of aged PECs de novo expressed the epithelial-to-mesenchymal transition markers α-smooth muscle and vimentin, with no changes in epithelial-to-mesenchymal transition markers E-cadherin and β-catenin. The mural cell markers neural/glial antigen 2, PDGF receptor-β, and CD146 as well as Notch 3 were also substantially increased in aged PECs. These data show that mice can be used to better understand the aging kidney and that PECs undergo substantial changes, especially in juxtamedullary glomeruli, that may participate in the overall decline in glomerular structure and function with advancing age.

KEYWORDS:

CD146; CD44; Notch 3; collagen type IV; epithelial-to-mesenchymal transition; extracellular signal-regulated kinase; glomerulosclerosis; glomerulus; heparan sulfate proteoglycan; neural/glial antigen 2; platelet-derived growth factor receptor-β; podocyte; vimentin; α-smooth muscle actin

PMID:
26017974
PMCID:
PMC4596731
DOI:
10.1152/ajprenal.00144.2015
[Indexed for MEDLINE]
Free PMC Article

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