Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis.
Nat Med
; 17(8): 952-60, 2011 Jul 31.
Article
em En
| MEDLINE
| ID: mdl-21804539
ABSTRACT
Focal segmental glomerulosclerosis (FSGS) is a cause of proteinuric kidney disease, compromising both native and transplanted kidneys. Treatment is limited because of a complex pathogenesis, including unknown serum factors. Here we report that serum soluble urokinase receptor (suPAR) is elevated in two-thirds of subjects with primary FSGS, but not in people with other glomerular diseases. We further find that a higher concentration of suPAR before transplantation underlies an increased risk for recurrence of FSGS after transplantation. Using three mouse models, we explore the effects of suPAR on kidney function and morphology. We show that circulating suPAR activates podocyte ß(3) integrin in both native and grafted kidneys, causing foot process effacement, proteinuria and FSGS-like glomerulopathy. Our findings suggest that the renal disease only develops when suPAR sufficiently activates podocyte ß(3) integrin. Thus, the disease can be abrogated by lowering serum suPAR concentrations through plasmapheresis, or by interfering with the suPAR-ß(3) integrin interaction through antibodies and small molecules targeting either uPAR or ß(3) integrin. Our study identifies serum suPAR as a circulating factor that may cause FSGS.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glomerulosclerose Segmentar e Focal
/
Integrina beta3
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Podócitos
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Receptores de Ativador de Plasminogênio Tipo Uroquinase
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
/
Adult
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Animals
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Female
/
Humans
/
Male
Idioma:
En
Revista:
Nat Med
Assunto da revista:
BIOLOGIA MOLECULAR
/
MEDICINA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos