Deficiency of PI3K enhances inflammation and fibrosis in experimental non alcoholic steatohepatitis but attenuates bile duct ligation induced fibrosis in vivo

Aims: Activation of hepatic stellate cells (HSC) results in collagen expression and liver fibrosis. We have shown in vitro that PI3K is part of the signalling pathway which leads to HSC activation and proliferation (Gäbele et al. JBC 2005). Here, we aimed to evaluate the role of PI3K in experimental NASH and BDL induced fibrosis. Methods and results: PI3K knockout mice (PI3K–/–) and wild-type control mice (WT; both on C57Bl/6 background) were randomly allocated to 4 experimental groups (n=6) receiving either standard chow (SC) or a high fat (HF) diet (17% fat, supplemented with 1.25% cholesterol and 0.5% cholate…