title: Compound effects of aging and experimental FSGS on glomerular epithelial cells.
abstract: Advanced age portends a poorer prognosis in FSGS. To understand the impact of age on glomerular podocytes and parietal epithelial cells (PECs), experimental FSGS was induced in 3m-old mice (20-year old human age) and 27m-old mice (78-year old human age) by abruptly depleting podocytes with a cytopathic anti-podocyte antibody. Despite similar binding of the disease-inducing antibody, podocyte density was lower in aged FSGS mice compared to young FSGS mice. Activated PEC density was higher in aged versus young FSGS mice, as was the percentage of total activated PECs. Additionally, the percentage of glomeruli containing PECs with evidence of phosphorylated ERK and EMT was higher in aged FSGS mice. Extracellular matrix, measured by collagen IV and silver staining, was higher in aged FSGS mice along Bowman's capsule. However, collagen IV accumulation in the glomerular tufts alone and in glomeruli with both tuft and Bowman's capsule accumulation were similar in young FSGS and aged FSGS mice. Thus, the major difference in collagen IV staining in FSGS was along Bowman's capsule in aged mice. The significant differences in podocytes, PECs and extracellular matrix accumulation between young mice and old mice with FSGS might explain the differences in outcomes in FSGS based on age.
authors.affiliation: Division of Nephrology, University of Washington, Seattle, WA 98109, USA.
authors.forename: Remington R S
authors.initials: RR
authors.lastname: Schneider
authors.affiliation: Division of Nephrology, University of Washington, Seattle, WA 98109, USA.
authors.forename: Diana G
authors.initials: DG
authors.lastname: Eng
authors.affiliation: Department of Applied Mathematics, University of Washington, Seattle, WA 98109, USA.
authors.forename: J Nathan
authors.initials: JN
authors.lastname: Kutz
authors.affiliation: Division of Nephrology, University of Washington, Seattle, WA 98109, USA.
authors.forename: Mariya T
authors.initials: MT
authors.lastname: Sweetwyne
authors.affiliation: Division of Nephrology, University of Washington, Seattle, WA 98109, USA.
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Pippin
authors.affiliation: Division of Nephrology, University of Washington, Seattle, WA 98109, USA.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Shankland
mesh_terms: D000367:Age Factors; D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D050476:Bowman Capsule / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism / Q000473:pathology*; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D010766:Phosphorylation; D050199:Podocytes / Q000378:metabolism / Q000473:pathology
chemical_list: D003094:Collagen
keywords: Collagen IV; epithelial to mesenchymal transition; glomerulus; kidney disease; parietal epithelial cell; podocyte