Evidences of the Presence of Hepatic Collagenase and its Changing Activity in Experimental Hepatic Fibrosis

Abstract

Marked absorption of collagen fibers has been observed after the discontinuation of noxic stimuli in experimental hepatic fibrosis or pre-cirrhosis induced by chronic carbon tetrachloride intoxication. The authors' enzymo-histochemical and electron microscopical study revealed that the collagen fibers would be degraded mainly in the extracellular process and the degraded fibers would be engulfed by the Kupffer cells and/or macrophages in the perisinusoidal spaces, and lysosomes within these mesenchymal cells would participate in digestion of the degraded collagen fibrils. So it was considered that hepatic collagenase may be present in the extracellular degradation of collagen fibers. However, collagenase has not been completely observed in the liver of animals and human being until authors reported in the Nature (252: 49, 1974).
Here is reported that the evidences of the presence of collagenase in rat liver and the changing activity of collagenase in the fibrotic and recovery stage in experimental hepatic fibrosis induced by carbon tetrachloride.
1. Using the culture method by Gross and Lapiere, collagenolytic activity which is active at neutral pH at 37°C and 35°C, employing the native reconstituted collagen fibrils was demonstrated in the fibrotic rat liver induced by chronic carbon tetrachloride intoxication.
2. This collagenolytic activity was identified with mammalian collagenase by disc electrophoretic patterns of reactive products.
3. Collagenase activity was very weak in the non-treated rat liver, but increased in the process of experimental hepatic fibrosis. In the cirrhotic stage, it decreased to the same extent of the non-treated rat liver.
4. In the recovery from experimental hepatic fibrosis, collagenase activity became maximal in 2 days after the discontinuation of carbon tetrachloride for 6 to 8 weeks when the histological findings showed no resorption of collagen fibers yet. And at 7 days after the discontinuation of noxic stimuli when the resorption of collagen fibers was extremely observed, it decreased to the same extent of the non-treated rat liver.
Collagenase would be the first attack enzyme on collagen fibers and play an important role in the collagen metabolism in the liver under physiological and pathological conditions.