Altered Proteoglycan Gene Expression in Human Biliary Cirrhosis

Proteoglycans play key roles in the physiological assembly of extracellular matrices and in the modulation of growth factor activities. During liver regeneration there is a profound remodelling of the connective tissue network with a concurrent alteration in proteoglycan gene expression. In the present study we have analyzed in detail the biochemical and molecular properties of the proteoglycans associated with biliary cirrhosis. The three major proteoglycans of human liver, namely decorin, syndecan and perlecan, were markedly elevated in the cirrhotic parenchyma as compared to normal liver tissue. Particularly elevated (eight fold) was the perlecan. This proteoglycan had not only heparan sulfate but also chondroitin and dermatan sulfate. Reverse transcriptase PCR revealed a marked enhancement of decorin and syndecan expression and detectable message for perlecan was found only in the cirrhotic liver. These results indicate that significant proteoglycan alterations are associated with the development of biliary cirrhosis and provide basis for future studies aimed at the characterization of the molecular events involved in the regulation of extracellular matrix deposition in this common human disease.