Reducing serum uric acid attenuates TGF-ß1-induced profibrogenic progression in type 2 diabetic nephropathy.
Nephron Exp Nephrol
; 121(3-4): e109-21, 2012.
Article
em En
| MEDLINE
| ID: mdl-23307286
ABSTRACT
BACKGROUND:
The pivotal role of transforming growth factor-ß1 (TGF-ß1)-induced tubulointerstitial fibrosis in the progression of chronic kidney disease is an active topic of research. Recent evidence indicates that hyperuricemia is associated with increased TGF-ß1 and progressive tubulointerstitial injury. We examined the hypothesis that lowering serum uric acid attenuates TGF-ß1-induced profibrogenic tubular change in type 2 diabetic nephropathy.METHODS:
KK-A(y)/Ta mice, an animal model of type 2 diabetes, were provided access to either regular drinking water or drinking water containing 10 mg/dl of allopurinol. Normal rat kidney epithelial cells were cultured and stimulated with 5 mM uric acid with or without allopurinol.RESULTS:
Type 2 diabetic mice that received allopurinol exhibited smaller increases in urinary albumincreatinine ratio than diabetic control mice, as well as attenuated TGF-ß1 and Smad pathway-induced profibrogenic tubular changes in diabetic kidneys. Allopurinol attenuated TGF-ß1-induced Smad pathway activation in tubular cells. These findings were related to increases in E-cadherin, and decreases in vimentin and α-smooth muscle actin. Uric acid-induced upregulation of TGF-ß1 depends on mitogen-activated protein kinase signaling.CONCLUSIONS:
This is the first study to demonstrate that reducing serum uric acid has preventive effects against to profibrogenic progression in type 2 diabetic kidney disease. These findings suggest that lowering serum uric acid may be an effective therapeutic intervention to prevent the progression of type 2 diabetic kidney disease.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácido Úrico
/
Progressão da Doença
/
Diabetes Mellitus Tipo 2
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Nefropatias Diabéticas
/
Fator de Crescimento Transformador beta1
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article