Collagenases and liver fibrosis

Hepatic lipocytes which are activated to a myofibroblastic phenotype synthesize many of the metalloproteinases and their inhibitors, particularly TIMP-1. The available evidence suggests that this enzyme/inhibitor system for regulating matrix degradation is important in liver in two respects; (i) degradation of the normal liver matrix by the gelatinases (A and B) and stromelysin and the role this has in the pathogenesis of liver injury, and (ii) failure of matrix degradation consequent upon the relative expression of interstitial collagenase and TIMP-1 by hepatic lipocytes and the role this has in the progression of liver fibrosis. Recent progress in this field provides a clear indication that liver fibrosis is dynamic, involving a balance between matrix synthesis and regulated matrix degradation. These observations offer opportunities for the development of new therapeutic strategies in the management of liver fibrosis.