title: Changes in glomerular parietal epithelial cells in mouse kidneys with advanced age.
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.
authors.affiliation: Division of Nephrology, University of Washington, Seattle, Washington; Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: Sebastian S
authors.initials: SS
authors.lastname: Roeder
authors.affiliation: Division of Nephrology, University of Washington, Seattle, Washington;
authors.forename: Ania
authors.initials: A
authors.lastname: Stefanska
authors.affiliation: Division of Nephrology, University of Washington, Seattle, Washington;
authors.forename: Diana G
authors.initials: DG
authors.lastname: Eng
authors.affiliation: Division of Nephrology, University of Washington, Seattle, Washington;
authors.forename: Natalya
authors.initials: N
authors.lastname: Kaverina
authors.affiliation: Division of Nephrology, University of Washington, Seattle, Washington;
authors.forename: Maria W
authors.initials: MW
authors.lastname: Sunseri
authors.affiliation: Division of Nephrology, University of Washington, Seattle, Washington;
authors.forename: Bairbre A
authors.initials: BA
authors.lastname: McNicholas
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington;
authors.forename: Peter
authors.initials: P
authors.lastname: Rabinovitch
authors.affiliation: Department of Nephropathology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany; and.
authors.forename: Felix B
authors.initials: FB
authors.lastname: Engel
authors.affiliation: Department of Nephropathology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany; and.
authors.forename: Christoph
authors.initials: C
authors.lastname: Daniel
authors.affiliation: Department of Nephropathology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany; and.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Amann
authors.affiliation: Division of Nephrology, University of Washington, Seattle, Washington;
authors.forename: Julia
authors.initials: J
authors.lastname: Lichtnekert
authors.affiliation: Division of Nephrology, University of Washington, Seattle, Washington;
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Pippin
authors.affiliation: Division of Nephrology, University of Washington, Seattle, Washington; stuartjs@uw.edu.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Shankland
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D050476:Bowman Capsule / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D018960:Hyaluronan Receptors / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology*; D008810:Mice, Inbred C57BL; D020286:Pericytes / Q000378:metabolism; D010766:Phosphorylation; D050199:Podocytes; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000378:metabolism
chemical_list: D015415:Biomarkers; C476399:Cd44 protein, mouse; D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; C499373:Notch3 protein, mouse; D000071656:Receptor, Notch3; D051880:Receptors, Notch; D048049:Extracellular Signal-Regulated MAP Kinases
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