DYNAMICS OF HEPATIC COLLAGEN-SYNTHESIS AND INTRACELLULAR DEGRADATION OF NEWLY SYNTHESIZED COLLAGEN DURING CHRONIC CARBON TETRACHLORIDE-INDUCED LIVER-INJURY IN RATS

To clarify the significance of intracellular degradation of newly synt hesized collagen during the progression of hepatic fibrosis, we measur ed the intracellular degradation of newly synthesized collagen at 2, 4 and 8 weeks after the administration of CCl4, together with the measu rement of collagen synthesis and serum prolyl hydroxylase concentratio n. Hepatic collagen synthesis and serum prolyl hydroxylase concentrati on did not change until 4 weeks after the CCl4 administration, but was increased significantly at 8 weeks. Intracellular degradation of newl y synthesized collagen was significantly increased at 2 weeks, was unc hanged at 4 weeks, and was significantly decreased at 8 weeks compared with the individual control. The percentage of the intracellular degr adation relative to the total amount of collagen synthesis did not cha nge at 2 and 4 weeks, but was significantly decreased at 8 weeks, comp ared with the controls. These results suggest that the intracellular d egradation system may prevent an accumulation of collagen at the early stage of hepatic injury, whereas at the stage of hepatic fibrosis, th e combination of an increase in collagen synthesis and a reduction of intracellular degradation may lead to a rapid accumulation of collagen .