title: Cells of renin lineage take on a podocyte phenotype in aging nephropathy.
abstract: Aging nephropathy is characterized by podocyte depletion accompanied by progressive glomerulosclerosis. Replacement of terminally differentiated podocytes by local stem/progenitor cells is likely a critical mechanism for their regeneration. Recent studies have shown that cells of renin lineage (CoRL), normally restricted to the kidney's extraglomerular compartment, might serve this role after an abrupt depletion in podocyte number. To determine the effects of aging on the CoRL reserve and if CoRL moved from an extra- to the intraglomerular compartment during aging, genetic cell fate mapping was performed in aging Ren1cCre × Rs-ZsGreen reporter mice. Podocyte number decreased and glomerular scarring increased with advanced age. CoRL number decreased in the juxtaglomerular compartment with age. There was a paradoxical increase in CoRL in the intraglomerular compartment at 52 and 64 wk of age, where a subset coexpressed the podocyte proteins nephrin, podocin, and synaptopodin. Transmission electron microscopy studies showed that a subset of labeled CoRL in the glomerulus displayed foot processes, which attached to the glomerular basement membrane. No CoRL in the glomerular compartment stained for renin. These results suggest that, despite a decrease in the reserve, a subpopulation of CoRL moves to the glomerulus after chronic podocyte depletion in aging nephropathy, where they acquire a podocyte-like phenotype. This suggests that they might serve as adult podocyte stem/progenitor cells under these conditions, albeit in insufficient numbers to fully replace podocytes depleted with age.
authors.affiliation: Division of Nephrology, University of Washington, Seattle, Washington;
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Pippin
authors.affiliation: Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York; and.
authors.forename: Sean T
authors.initials: ST
authors.lastname: Glenn
authors.affiliation: Division of Nephrology, University of Washington, Seattle, Washington;
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Krofft
authors.affiliation: Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York; and.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Rusiniak
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Alpers
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington.
authors.forename: Kelly
authors.initials: K
authors.lastname: Hudkins
authors.affiliation: Division of Nephrology, University of Washington, Seattle, Washington;
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Duffield
authors.affiliation: Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York; and.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Gross
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; D002452:Cell Count; D002460:Cell Line; D019070:Cell Lineage; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism / Q000473:pathology*; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D050199:Podocytes / Q000378:metabolism / Q000473:pathology*; D012083:Renin / Q000235:genetics* / Q000378:metabolism
chemical_list: D012083:Renin
keywords: cells of renin lineage; focal segmental glomerulosclerosis; glomerulus; podocyte; regeneration