C 型肝炎病毒（hepatitis C virus）的長期慢性感染會導致肝臟纖維化，進而造成肝硬化。研
究指出此病毒之套膜蛋白E2 與細胞膜上的CD81 結合後，會藉由ERK/MAPK 的途徑活化
轉錄因子AP-2，進而導致MMP-2 的蛋白表現量以及活性上升，顯示E2 可能與HCV 導致
的纖維化有關。因此本計畫將E2 基因送入HSC 中，利用RT-PCR 以及西方墨點法來進一
步分析，證實E2 可導致HSC 活化，並影響若干纖維化相關因子的mRNA 以及蛋白表現量，
包括α-SMA、Collagen α (I)、interleukin (IL)-6、IL-10、IL-1β、TGF-β1、connective tissue growth
factor (CTGF)、MMP-2 等。最後再利用E2 的siRNA 處理後，觀察纖維化相關因子的影響，
更進一步證實之前的研究成果。
Chronic infection of hepatitis C virus (HCV) may lead to hepatic fibrosis and subsequently
cirrhosis, however, the underlying mechanisms have not been established. Previous studies
have indicated that the binding of HCV E2 protein and CD81 on the surface of HSC may
activate ERK/MAPK pathway to enhance the expression of the transcriptional factor, AP-2,
which subsequently lead to the increased protein level and activity of MMP-2. Therefore in this
study, full-length E2 gene was transiently transfected into HSC cells and the mRNA and protein
levels of fibrosis-related molecules, including α-SMA, Collagen α (I), IL-6, IL-10, IL-1β,
TGF-β1, CTGF, MMP-2, and TIMP-1 were analyzed to evaluate the impact of E2 on fibrosis.
Furthermore, a pre-treatment with siRNA for E2, was employed to see if it may abolish the
E2-induced fibrosis by determining the mRNA and protein levels of studied fibrosis-related
molecules. Results from this study soundly proved that the expression of HCV E2 may induce
fibrosis of HSC cells.
