Abstract

Fibrotic lesions affect a wide variety of organs but liver fibrosis is probably the most abundant form of organ fibrosis. Disturbances of the equilibrium between parenchyma and extracellular matrix (ECM) leading to a disproportionate increase and irregular deposition of newly formed connective tissue components (fibrosis) is a common and clinically most important sequelae of chronic active liver diseases. Significant progress has been made during the last years in the analysis of the structural composition of ECM in normal and fibrotic liver and in the dissection of the molecular and cellular mechanisms of exaggerated ECM-deposition in necroinflammatory areas using experimental models of hepatic fibrosis, isolated cells in mono- and coculture systems and the growing repertoire of molecular biological tools. Perisinusoidal, retinoid-storing cells (Ito cells, parasinusoidal lipocytes) transform under inflammatory stimuli to myofibroblast-like cells being qualitatively and quantitatively the most important connective tissue producing cell type in human and animal liver. Its activation and transformation is mediated by paracrine and autocrine loops involving transforming growth factor (TGF) beta as the main fibrogenic mediator secreted by activated liver macrophages, possibly also by endothelial cells and liberated by disintegrated thrombocytes. In advanced stages of retinoid-storing cell transformation additional growth factors like platelet derived growth factor (PDGF) become important indicating a sequential action of cytokines and fibrogenic mediators during the fibrogenic process. The molecular and cellular interactions in the course of liver fibrogenesis have gained model character for a number of other organ fibrotic processes, wound repair, and atherogenesis included.(ABSTRACT TRUNCATED AT 250 WORDS)