Experimental and human liver fibrogenesis

In this work, we provide an overview of our results obtained by studying th e role of transforming growth factor beta 1 and proteoglycans in liver fibr ogenesis. It has been found that transforming growth factor beta 1 is one o f the most important stimulators of extracellular matrix synthesis in the l iver. In chronic liver injury, desmin-positive non-parenchymal liver cells expressed transforming growth factor beta 1. The extracellular localization of the growth factor correlated well with types I, III and IV procollagen- alpha, which were detected in the fibrous septa of chronically injured live rs. A similar distribution pattern was observed in human specimens. To iden tify the role of transforming growth factor beta 1 in liver extracellular m atrix protein synthesis, transforming growth factor beta 1-positive transge nic mice were generated. Animals expressing the growth factor in their live r showed spontaneous liver fibrosis. Proteoglycans also participate in fibr ogenesis. The majority of liver-specific heparan sulfate proteoglycans, suc h as syndecan-1 and fibroglycan, are produced by hepatocytes. The extracell ular matrix proteoglycans decorin and perlecan are synthesized by non-paren chymal liver cells. The amount of the latter is very low in normal liver, b ut increases dramatically in Liver fibrosis. The effect of regulatory facto rs on liver proteoglycans seems to be cell type-specific. In contrast to pr evious observations, elevated amounts of decorin did not inhibit the action of transforming growth factor beta 1 in the liver.