Development of an in vitro Model to Study Hepatitis C virus-induced Fibrosis

Abstract

Aim: To investigate the mechanism of liver fibrosis in chronic hepatitis C virus (HCV) infection we developed an in vitro model. Methods: Huh7 cells were transfected with HCV (JFH1 or Jc1) or sub-genomic replicons and expression of pro-fibrotic cytokines determined by qPCR. Media from infected cells was transferred onto LX2 cells or primary rat stellate cells and expression of pro-fibrotic genes measured by qPCR. Results: Replication competent HCV, but not sub-genomic replicons, induced expression of TGF-β1 and CTGF. Supernatant from infected cells induced α-SMA and COL1A1 expression and stellate cell migration, confirming functional activation. Conclusion: Infected cells produce pro-fibrogenic cytokines TGF-β1 and CTGF and activate stellate cells. This mechanism could be targeted to prevent or treat HCV-induced fibrosis.