Effect of Notch signaling on the activation of hepatic stellate cells / 中华肝脏病杂志
Chinese Journal of Hepatology
; (12): 677-682, 2012.
Article
em Zh
| WPRIM
| ID: wpr-296829
Biblioteca responsável:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To investigate whether Notch signaling is activated in hepatic stellate cells (HSCs), and to determine whether manipulation of the Notch signaling pathway can effect the activation of HSCs.</p><p><b>METHODS</b>The expression of Notch signaling components in unactivated or TGF-b1-activated HSC-T6 cells was detected by Taqman Probe-based gene expression analysis. Differential expression of Notch3 and Jagged1 was detected by immunofluorescence analysis. Notch3-mediated expression of the myofibroblastic markers, a-SMA and collagen I, was detected in HSC-T6 cells transfected with pcDNA3.1-N3ICD or Notch3 siRNA by Western blotting.</p><p><b>RESULTS</b>Notch signaling components were expressed in both unactivated and activated HSC-T6 cells, but the TGF-b1-treated cells showed significantly higher expression levels of Jagged1 (3.9-fold, F = 2543.482), Notch3 (4.2-fold, F = 287.982), and HES1 (3.2-fold, F = 1719.851). Transfection-mediated over-expression of Notch3 led to significantly increased expression of a-SMA (6.8-fold, t = 13.157) and collagen I (5.5-fold, t = 9.810) (both P less than 0.01). Transient knock-down of Notch3 expression by siRNA decreased expression of the myofibroblastic markers (a-SMA by approximately 90%, t = 19.863 and collagen I by 84%, t = 10.376; both, P less than 0.01). Moreover, knock-down of Notch3 antagonized the TGF-b1-induced expression of a-SMA and collagen I.</p><p><b>CONCLUSION</b>Notch signaling may participate in liver fibrogenesis by regulating HSC activation. Selective interruption of Notch3 may represent a new anti-fibrotic strategy to treat liver fibrosis.</p>
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Índice:
WPRIM
Assunto principal:
Proteínas de Ligação ao Cálcio
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RNA Mensageiro
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Transdução de Sinais
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Linhagem Celular
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Peptídeos e Proteínas de Sinalização Intercelular
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RNA Interferente Pequeno
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Receptores Notch
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Células Estreladas do Fígado
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Proteínas Serrate-Jagged
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Proteína Jagged-1
Limite:
Animals
Idioma:
Zh
Revista:
Chinese Journal of Hepatology
Ano de publicação:
2012
Tipo de documento:
Article