Fluorofenidone suppresses epithelial-mesenchymal transition and the expression of connective tissue growth factor via inhibiting TGF-beta/Smads signaling in human proximal tubular epithelial cells.
Pharmazie
; 66(12): 961-7, 2011 Dec.
Article
em En
| MEDLINE
| ID: mdl-22312703
ABSTRACT
OBJECTIVES:
The present study was designed to investigate the potential effects and mechanism of fluorofenidone (AKF-PD) on transforming growth factor beta1 (TGF-beta1)-induced tubular epithelial-mesenchymal transition (EMT) and the expression of connective tissue growth factor (CTGF) in human proximal tubular epithelial cells.METHODS:
HK-2 cells were pretreated with AKF-PD, pirfenidone (PFD), Losartan, and SB431542 (an inhibitor of TGF-beta type I receptor). The pretreated HK-2 cells were subsequently co-treated with TGF-beta1 (5 ng/ml). The morphological changes of HK-2 cells were observed under an inverted microscope. Expression of alpha-SMA was detected by Western blot and immunofluorescence. The protein expression of ZO-1, fibronectin, CTGF, phosphorylated Smad2 (p-Smad2) and phosphorylated Smad3 (p-Smad3) were evaluated by Western blot.RESULTS:
Through down-regulation of p-Smad2 and p-Smad3 proteins, AKF-PD significantly inhibited protein expression of alpha-SMA, fibronectin, and CTGF. Meanwhile, the depressed ZO-1 expression and morphological changes induced by TGF-beta1 were attenuated by AKF-PD.CONCLUSION:
AKF-PD acts as an anti-fibrotic agent through blocking TGF-beta/Smads signaling and consequently inhibits TGF-beta1-induced EMT and CTGF expression in human proximal tubular epithelial cells.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piridonas
/
Fator de Crescimento Transformador beta
/
Proteínas Smad
/
Fator de Crescimento do Tecido Conjuntivo
/
Transição Epitelial-Mesenquimal
/
Túbulos Renais Proximais
Limite:
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article