Expression of decorin, transforming growth factor-beta1, tissue inhibitor metalloproteinase 1 and 2, and type IV collagenases in chronic hepatitis

Decorin is a small extracellular matrix proteoglycan. It binds and modulate s transforming growth factor (TGF)-beta1 action, the major stimulator of fi brogenesis. Its role in the pathogenesis of human liver cirrhosis is unknow n. Therefore, we studied the relationship of the 2 proteins in normal human liver and in 43 chronic hepatitis and liver cirrhosis specimens. To unders tand the mechanism that maintains matrix deposition in stage IV hepatitis, we studied expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2, as well as the activities of type IV collagenases. Gene expression was analyzed on messenger RNA and protein level by morphologic and biochem ical approaches. Decorin proved to be an early marker of fibrogenesis, and its deposition in creased parallel to that of TGF-beta1 and to inflammatory activity. Liver f ibrosis progressed despite high temporospatial expression of decorin with T GF-beta1. Neither decorin nor TGF-beta1 protein deposition increased furthe r in cirrhosis with low inflammatory activity, suggesting that impaired ext racellular matrix catabolism rather than active production plays a role in this stage. This possibility was supported by high message levels of metall oproteinase inhibitors, no 72-kd collagenase activities, and low 92-kd coll agenase activities.