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Acta Virologica Vol.60, No.3, p.242-248, 2016 |
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Title: The possible role of NS3 protease activity of hepatitis C virus on fibrogenesis and miR-122 expression in hepatic stellate cells | ||
Author: S. KHANIZADEH, M. RAVANSHAD, S. Y. HOSSEINI, P. DAVOODIAN, A. N. ZADEH, F. SABAHI, J. SARVARI, Z. KHANLARI, M. HASANI-AZAD | ||
Abstract: The various roles of hepatitis C virus (HCV) NS3 protein in viral pathogenesis are emphasized, especially in the progression of fibrosis and tumors. The levels of miR-122 have been widely accepted as a critical factor in viral pathogenesis and disease progression. However, the possible correlation between miR-122 levels and fibrosis state has been less investigated. Therefore, in this study, plasmids expressing protease competent and protease mutated non-structural proteins 3 (NS3) were transfected into LX-2 cell line. Subsequently, the total RNA was extracted and real-time PCR was performed to measure the expression level of miR-122, collagen type 1 alpha 1 (COL1A1), alpha smooth muscle actin (α-SMA), and tissue inhibitor of metaloproteinase 1 (TIMP-1). Moreover, the transforming growth factor beta (TGF-β) levels in the supernatants of transfected cells were evaluated by ELISA. The gene expression analysis of fibrotic genes and TGF-β cytokine in LX-2 cells showed that protease competent NS3 had a significant fibrogenic impact when compared to protease defective NS3 or GFP control plasmids (P <0.001). The results also demonstrated that the expression of miR-122 was downregulated in both versions of the cells transfected with NS3 plasmids (P <0.01) irrespective of protease function. These results suggested that the protease function of NS3 protein is a crucial factor for the induction of hepatic fibrosis but it doesn't play a complete role in the expression of miR-122. |
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Keywords: HCV; miRNA; fibrosis; HSCs; NS3; protease; miR-122 | ||
Published online: 13-Sep-2016 | ||
Year: 2016, Volume: 60, Issue: 3 | Page From: 242, Page To: 248 | |
doi:10.4149/av_2016_03_242 |
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