|
KMID : 0357920090430060503
|
|
Korean Journal of Pathology
2009 Volume.43 No. 6 p.503 ~ p.508
|
|
|
Transcriptional Regulation of Hepatic Stellate Cell Activation by siRNA for TGF-β1
|
|
Oh Hoon-Kyu
Park Kwan-Kyu
Park Jae-Bok
Cho Chang-Ho
Kim Kyung-Hyun
Kum Yoon-Seup
|
|
|
Abstract
|
|
|
Background: The cytokine-induced activation of hepatic stellate cells (HSC) plays a major role in liver fibrosis. Quiescent HSCs undergo phenotypic transformation called "transdifferentiation" in response to viral, chemical or immune insults to the liver. The cytokine TGF-β1 plays a key role in progressive liver fibrosis. Since small interfering RNA (siRNA) is a powerful tool for silencing gene expression post-transcriptionally, the present study aimed to determine whether synthetic TGF-β1 siRNA down-regulates the expression of the TGF-β1 gene in immortalized and activated rat HSCs (HSC-T6s). The study examined whether synthetic TGF-β1 siRNA prevents rat HSCs activation and extracellular matrix (ECM) production.
Methods: TGF-β1 siRNA or a control (pU6) siRNA was added to HSC-T6 culture media. We then performed RT-PCR and western blot analyses for TGF-β1 and ECM components (fibronectin, type-I collagen, and TIMP-1).
Results: TGF-β1 siRNA significantly down-regulated expression of TGF-β1 mRNA and protein and attenuated mRNA and protein expressions of type-I collagen, fibronectin, and TIMP-1, as compared to the control.
Conclusions: TGF-β1 siRNA can effectively down-regulate the expression of TGF-β1 in rat HSC, resulting in significant inhibition of HSC activation and of ECM production. These data indicate that synthetic TGF-β1 siRNA can be a useful treatment modality to prevent liver fibrosis.
|
|
|
KEYWORD
|
|
|
Transforming growth factor-beta, Small interfering RNA, Hepatic stellate cell, Liver fibrosis
|
|
|
FullTexts / Linksout information
|
|
 
|
|
|
Listed journal information
|
|
  
|