Background/aims: Matrix metalloproteinase-13, one of the principal neutral proteinases capable of cleaving native fibrillar collagens, is important in the degradation and remodeling of extracellular matrix. However, its precise expression in liver injury has not been characterized. We examined the kinetics of the expression of matrix metalloproteinase-13 and one of its specific inhibitors, tissue inhibitor of metalloproteinase-1, in acute liver injury in rats.
Methods: Acute liver injury was induced by administration of carbon tetrachloride or two different doses of D-galactosamine hydrochloride in Wistar rats. Hepatic matrix metalloproteinase-13 and tissue inhibitor of metalloproteinase-1 mRNA levels were then examined by Northern blotting.
Results: All rats survived after liver injury induced by carbon tetrachloride or low doses of D-galactosamine hydrochloride. However, rats died 5 days after induction of liver injury by high doses of D-galactosamine hydrochloride. In carbon tetrachloride-induced liver injury, matrix metalloproteinase-13 mRNA was transiently increased between 6 h and 1 day after injury. Tissue inhibitor of metalloproteinase-1 mRNA expression was increased between 6 h and 3 days after the peak of matrix metalloproteinase-13 expression. Similar patterns of matrix metalloproteinase-13 and tissue inhibitor of metalloproteinase-1 expression were observed in low-dose D-galactosamine hydrochloride-induced liver injury. In contrast, in high-dose D-galactosamine hydrochloride-induced liver injury, tissue inhibitor of metalloproteinase-1 expression peaked before matrix metalloproteinase-13 expression, which was increased 2 days after injury. Both mRNA levels continued to increase until death.
Conclusions: Transient expression of matrix metalloproteinase-13, followed by that of tissue inhibitor of metalloproteinase-1, was observed during recovery from acute liver injury induced by carbon tetrachloride and low-dose D-galactosamine hydrochloride. In contrast, disordered expression of matrix metalloproteinase-13 was observed in fatal liver injury caused by high-dose D-galactosamine hydrochloride. These results indicate that matrix metalloproteinase13 plays an important role in the early phase of recovery from liver injury.