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-beta1 and CTGF. Supernatant from infected cells induced alpha-SMA and COL1A1 expression and stellate cell migration, confirming functional activation. CONCLUSIONS: Infected cells produce pro-fibrogenic cytokines TGF-beta1 and CTGF and activate stellate cells. This mechanism could be targeted to prevent or treat HCV-induced fibrosis.