Role of connective growth factor in plasminogen activator inhibitor-1 and fibronectin expression induced by transforming growth factor beta1 in renal tubular cells / 中华医学杂志(英文版)
Chinese Medical Journal
; (24): 990-996, 2004.
Article
en En
| WPRIM
| ID: wpr-284863
Biblioteca responsable:
WPRO
ABSTRACT
<p><b>BACKGROUND</b>Connective tissue growth factor (CTGF) contributes greatly to renal tubulointerstitial fibrosis, which is the final event leading to end-stage renal failure. This study was designed to investigate the effects of CTGF antisense oligodeoxynucleotides (ODNs) on the expressions of plasminogen activator inhibitor-1 (PAI-1) and fibronectin in renal tubular cells induced by transforming growth factor beta1 (TGF-beta1) in addition to the role of CTGF in the accumulation and degradation of renal extracellular matrix (ECM).</p><p><b>METHODS</b>A human proximal tubular epithelial cell line (HKC) was cultured in vitro. Cationic lipid-mediated CTGF antisense ODNs were transfected into HKC cells. After HKC cells were stimulated with TGF-beta1 (5 microg/L), the mRNA levels of PAI-1 and fibronectin were measured by RT-PCR. Intracellular PAI-1 protein synthesis was assessed by flow cytometry. The secreted PAI-1 and fibronectin in the medium were determined by Western blot and ELISA, respectively.</p><p><b>RESULTS</b>TGF-beta1 was found to induce tubular CTGF, PAI-1, and fibronectin mRNA expression. PAI-1 and fibronectin mRNA expression induced by TGF-beta1 was significantly inhibited by CTGF antisense ODNs. CTGF antisense ODNs also inhibited intracellular PAI-1 protein synthesis and lowered the levels of PAI-1 and fibronectin protein secreted into the medium.</p><p><b>CONCLUSIONS</b>CTGF may play a crucial role in the accumulation and degradation of excessive ECM during tubulointerstitial fibrosis, and transfecting CTGF antisense ODNs may be an effective way to prevent renal fibrosis.</p>
Texto completo:
1
Base de datos:
WPRIM
Asunto principal:
Farmacología
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Fisiología
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ARN Mensajero
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Transfección
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Células Cultivadas
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Oligonucleótidos Antisentido
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Factor de Crecimiento Transformador beta
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Fibronectinas
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Inhibidor 1 de Activador Plasminogénico
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Proteínas Inmediatas-Precoces
Límite:
Humans
Idioma:
En
Revista:
Chinese Medical Journal
Año:
2004
Tipo del documento:
Article