Dynamics of hepatic collagen synthesis and intracellular degradation of newly synthesized collagen during chronic carbon tetrachloride-induced liver injury in rats.

Abstract

To clarify the significance of intracellular degradation of newly synthesized collagen during the progression of hepatic fibrosis, we measured the intracellular degradation of newly synthesized collagen at 2, 4 and 8 weeks after the administration of CCl4, together with the measurement of collagen synthesis and serum prolyl hydroxylase concentration. Hepatic collagen synthesis and serum prolyl hydroxylase concentration did not change until 4 weeks after the CCl4 administration, but was increased significantly at 8 weeks. Intracellular degradation of newly synthesized collagen was significantly increased at 2 weeks, was unchanged at 4 weeks, and was significantly decreased at 8 weeks compared with the individual control. The percentage of the intracellular degradation relative to the total amount of collagen synthesis did not change at 2 and 4 weeks, but was significantly decreased at 8 weeks, compared with the controls. These results suggest that the intracellular degradation system may prevent an accumulation of collagen at the early stage of hepatic injury, whereas at the stage of hepatic fibrosis, the combination of an increase in collagen synthesis and a reduction of intracellular degradation may lead to a rapid accumulation of collagen.