کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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3424991 | 1227263 | 2011 | 13 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Hepatitis C virus-induced furin and thrombospondin-1 activate TGF-β1: Role of TGF-β1 in HCV replication Hepatitis C virus-induced furin and thrombospondin-1 activate TGF-β1: Role of TGF-β1 in HCV replication](/preview/png/3424991.png)
In this study, we demonstrated the molecular mechanisms of TGF-β1 induction as well as proteolytic activation in HCV (JFH-1)-infected cells. Our studies showed the synthesis and secretion of TGF-β1 in HCV-infected cells which was reduced in the presence of Ca2+ chelators, an inhibitor of mitochondrial Ca2+ uptake, and antioxidants. We also showed that the expression of HCV NS proteins NS3/4A, and NS5A can induce TGF-β1 by cell-based luciferase assay. Furthermore, mutational analysis revealed that the functionally active protease domain of NS3 and N-terminus domain of NS5A are required for TGF-β1 activity. Using siRNA approach we demonstrated that HCV-induced furin and thrombospondin-1 (TSP-1) are involved in the proteolytic activation of TGF-β1. Our results also suggest that TGF-β1 positively regulates HCV RNA replication. Collectively, these observations provide insight into the mechanism of TGF-β1 activation, which likely manifest in liver fibrosis associated with hepatitis C infection.
Journal: Virology - Volume 412, Issue 2, 10 April 2011, Pages 284–296