ABSTRACT

This chapter describes the two elements which are crucial to the understanding of collagen synthesis: the level of gene regulation responsible for changes in collagen content and factors that affect collagen gene expression. An increase in collagen content plays a direct role in the pathophysiology of chronic liver disease through its effect on both hepatic structure and function. The increased level of procollagen mRNAs that is associated with an increase in hepatic collagen content in fibrosis is strong evidence that an enhanced synthesis of the protein is the primary mechanism for the pathological state, rather than a decrease in the degradation of the protein. The nuclear run-on assay has been employed to investigate transcriptional rates of the collagens and other hepatic genes. The extremely low concentration at which TGF-ß1 exerts its effects on hepatocytes in culture and its possible regulatory role in matrix formation have led us to investigate this cytokine for its possible role in hepatic fibrogenesis.