Fluorofenidone attenuates tubulointerstitial fibrosis by inhibiting TGF-ß(1)-induced fibroblast activation.
Am J Nephrol
; 34(2): 181-94, 2011.
Article
em En
| MEDLINE
| ID: mdl-21791914
ABSTRACT
BACKGROUND:
Novel therapeutic agents are urgently needed to combat renal fibrosis. The purpose of this study was to assess, using complete unilateral ureteral obstruction (UUO) in rats, whether fluorofenidone (AKF-PD) [1-(3-fluorophenyl)-5-methyl-2-(1H)-pyridone] inhibits renal fibrosis, and to determine whether it exerts its inhibitory function on renal fibroblast activation.METHODS:
Sprague-Dawley rats were randomly divided into 3 groups sham operation, UUO and UUO/AKF-PD (500 mg/kg/day). Renal function, tubulointerstitium damage index score, extracellular matrix (ECM) deposition, and the expressions of TGF-ß(1), collagen III, α-SMA, p-Smad2, p-Smad3, p-ERK1/2, p-JNK and p-p38 were measured. In addition, the expressions of α-SMA, fibronectin, CTGF, p-Smad2/3, p-ERK1/2, p-p38 and p-JNK were measured in TGF-ß(1)-stimulated normal rat renal fibroblasts (NRK-49F).RESULTS:
AKF-PD treatment significantly attenuated tubulointerstitium damage, ECM deposition, the expressions of TGF-ß(1), collagen III, α-SMA, p-ERK1/2, p-p38 and p-JNK in vivo. In vitro, AKF-PD dose-dependently inhibited expressions of α-SMA, fibronectin and CTGF. Furthermore, AKF-PD did not inhibit Smad2/3 phosphorylation or nuclear accumulation, but rather attenuated ERK, p38 and JNK activation.CONCLUSION:
AKF-PD treatment inhibits the progression of renal interstitial fibrosis in obstructed kidneys; this is potentially achieved by suppressing fibroblast activation. Therefore, AKF-PD is a special candidate for the treatment of renal fibrosis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piridonas
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Fibrose
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Regulação da Expressão Gênica
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Fator de Crescimento Transformador beta1
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Fibroblastos
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Túbulos Renais
Limite:
Animals
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article