| Abstract: | The dynamics of hepatic collagen biosynthesis and degradation were studied in mice infected with Schistosoma japonicum. Hepatic fibrosis, the major clinical manifestation of disease, increased during acute infection (0-15 wk). The majority of proline incorporation into hydroxyproline, which was reflective of collagen synthesis, was found within hepatic egg granulomas. As the disease became chronic (20-30 wk) there was a decrease in collagen synthesis and a maintenance of total collagenolytic activity, which resulted in decreased accumulations of both total hepatic and granuloma-associated collagen. In addition to these quantitative decreases in extracellular collagen there was a qualitative change in the type of hepatic collagen synthesized. Early in infection, type I collagen was the predominant biosynthetic product, whereas late in infection type III collagen became the dominant isotype. A similar switch was seen in the substrate specificity of the constitutive collagenolytic activity, with decreasing type I activity and increasing type III activity as the disease progressed from acute (10 wk) to chronic (30 wk). These changes in the quantity and makeup of extracellular collagen may lead to amelioration of disease and potential reversibility of fibrosis. |
