간성상세포의 활성에서 siRNA를 이용한 TGF-b1의 전사조절
Transcriptional Regulation of Hepatic Stellate Cell Activation by siRNA for TGF-β1
오훈규, 박관규, 박재복, 조창호, 김경현, 금윤섭,
소속 상세정보
오훈규 ( Oh Hoon-Kyu )
대구가톨릭대학교 의과대학 병리학교실
박관규 ( Park Kwan-Kyu )
대구가톨릭대학교 의과대학 병리학교실
박재복 ( Park Jae-Bok )
대구가톨릭대학교 의과대학 병리학교실
조창호 ( Cho Chang-Ho )
대구가톨릭대학교 의과대학 병리학교실
김경현 ( Kim Kyung-Hyun )
대구가톨릭대학교 의과대학 병리학교실
금윤섭 ( Kum Yoon-Seup )
대구가톨릭대학교 의과대학 병리학교실
KMID : 0357920090430060503
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.
키워드
Transforming growth factor-beta;Small interfering RNA;Hepatic stellate cell;Liver fibrosis
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