Type VI collagen is a minor but essential matrix component in the liver. In this study, we utilized an acute and a chronic injury model to clarify the process of
liver fibrosis in rats by administration of
carbon tetrachloride.
Collagen gene expression, with particular emphasis on
type VI collagen, was studied by molecular hybridization techniques. The alpha 2(VI)
collagen mRNA levels were markedly elevated on day 3 of acute injury and were approximately at the same high level at 7 and 14 weeks of chronic injury, as determined by Northern hybridizations and slot-blot analyses. Marked enhancement of
type I collagen gene expression was similarly noted at these time points. The activation of
collagen gene expression in acute injury, as determined by in situ hybridization, was particularly prominent in the vicinity of the central veins. Indirect immunofluorescence demonstrated marked accumulation of
type VI collagen protein as early as day 3 of acute injury, and the reaction appeared to be initiated in the proximity of central veins. These results indicate that
type VI collagen gene expression, together with other connective tissue components, including
type I collagen, is activated in the early stages of the fibrotic process.
Type VI collagen accumulation may contribute to the distorted architecture and functional impairment of the liver in hepatic
fibrosis.