Halofuginone stimulates interstitial collagenase activity in HSC via activation of p38 and nuclear factor kappa B

Aims: The semisynthetic plant alkaloid Halofuginone (HAL) was reported to be a specific inhibitor of procollagen I expression and shown to ameliorate thioacetamide-induced rat liver fibrosis. We recently found that the antifibrotic potential of HAL is likely to be associated with a strong MMP induction in activated hepatic stellate cells (HSC). Our present study aimed to investigate molecular mechanisms involved in this effect. Methods: The HSC line CFSC-2G and isolated rat HSC were incubated with increasing concentrations of HAL. mRNA steady state levels of MMP-3, -13 were quantified by real-time PCR. Interstit…