| Literature DB >> 21296375 |
Lance D Presser1, Adam Haskett, Gulam Waris.
Abstract
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 Ca(2+) chelators, an inhibitor of mitochondrial Ca(2+) 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.Entities:
Mesh：
Substances：
Year: 2011 PMID： 21296375 PMCID： PMC3073624 DOI： 10.1016/j.virol.2010.12.051
Source DB: PubMed Journal: Virology ISSN： 0042-6822 Impact factor: 3.616