Dimethylnitrosamine administration induces a rapid increase in
collagen deposition with concomitant proliferation of hepatic stellate cells in rats. Here, we investigated the pathophysiological profiles of acute and chronic hepatic
fibrosis states and attempted to determine the possible role of Kruppel-like factor-5 (KLF5) in this model. In acute study using a single
drug injection, we observed a rapid transient increase of ALT and
mRNA levels of KLF5 followed by increases in
fibrosis-related genes. Repeated administration of
dimethylnitrosamine once a week caused early damage with severe
fibrosis and sustained hepatocyte injury, while intermittent
injections at 2-week intervals induced only modest
fibrosis from 3 weeks. Weekly administration also induced profound upregulation of
collagen I, alpha-smooth muscle actin, and KLF5
mRNA. In contrast, such continued augmentation was not observed after intermittent
injections; KLF5 increased only after 3 weeks. These results suggested that
dimethylnitrosamine induced a rapid hepatic fibrogenic response with a possible participation of KLF5.