title: Interstitial pericytes decrease in aged mouse kidneys.
abstract: With increasing age, the kidney undergoes characteristic changes in the glomerular and tubulo-interstitial compartments, which are ultimately accompanied by reduced kidney function. Studies have shown age-related loss of peritubular vessels. Normal peritubular vessel tone, function and survival depend on neighboring pericytes. Pericyte detachment leads to vascular damage, which can be accompanied by their differentiation to fibroblasts and myofibroblasts, a state that favors matrix production. To better understand the fate of pericytes in the aged kidney, 27 month-old mice were studied. Compared to 3 month-old young adult mice, aged kidneys showed a substantial decrease in capillaries, identified by CD31 staining, in both cortex and medulla. This was accompanied by a marked decrease in surrounding NG2+ / PDGFRβ+ pericytes. This decrease was more pronounced in the medulla. Capillaries devoid of pericytes were typically dilated in aged mice. Aged kidneys were also characterized by interstitial fibrosis due to increased collagen-I and -III staining. This was accompanied by an increase in the number of pericytes that acquired a pro-fibrotic phenotype, identified by increased PDGFRβ+ / αSMA+ staining. These findings are consistent with the decline in kidney interstitial pericytes as a critical step in the development of changes to the peritubular vasculature with aging, and accompanying fibrosis.
authors.affiliation: Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA 98104, USA.
authors.forename: Ania
authors.initials: A
authors.lastname: Stefanska
authors.affiliation: Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA 98104, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Eng
authors.affiliation: Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA 98104, USA.
authors.forename: Natalya
authors.initials: N
authors.lastname: Kaverina
authors.affiliation: Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA 98104, USA.|Biogen Idec, Cambridge, MA 02142, USA.
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Duffield
authors.affiliation: Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA 98104, USA.
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Pippin
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Rabinovitch
authors.affiliation: Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA 98104, USA.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Shankland
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D000941:Antigens / Q000235:genetics / Q000378:metabolism; D002196:Capillaries / Q000033:anatomy & histology / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D007668:Kidney / Q000098:blood supply* / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D020286:Pericytes / Q000166:cytology*; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism; D051437:Renal Insufficiency; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D011509:Proteoglycans; D020797:Receptor, Platelet-Derived Growth Factor beta; D000099216:Chondroitin Sulfate Proteoglycan 4
keywords: NG2; PDGFβ-receptor; endothelium; nephropathy; tubulo-interstitial fibrosis