Purpose: Hepatic stellate cells (HSC), known as Ito cells, are important cells in the hepatic fibrogenesis. Through activation, HSCs transdifferentiate to myofibroblasts and produce extracellular matrix and induce tissue remodeling. The aim of this study is to inhibit the activation of HSC by STI571 to treat liver cirrhosis in mice.Materials and
Methods: C3H mice were treated with CCl4 2.0 gm/kg two times per week for 6 weeks. STI571 was used to treat mice by intra-peritoneal injection for one week. Four groups were designed: (1) no treatment, (2) with STI571, (3) CCl4 treatment, and (4) both CCl4 and STI-571). The mice were euthanized to check the histology and liver proliferation.
Results: STI571 has good antifibrotic effect in HE and Trichrome staining. This is also demonstrated in SMA immunohistochemistry. The apoptosis staining showed more positive in CCl4 group (3). In primary cell culture, HSCs showed lower proliferation activity with STI571 treatment and the cytoskeleton production in confocal microscopy. The extracellular matrix ( procollagen (I)) production was also decreased in STI571 treated group.
Conclusion: STI571 is effective to reverse the fibrogenesis in vivo and in vitro. This mechanism through tyrosine kinase inhibitors induce lower proliferation and higher apoptosis of HSC.