Structure of the extracellular matrix in normal and fibrotic liver: collagens and glycoproteins.

The sketches in Figures 11 and 12, necessarily simplified, summarize some of the points discussed in the previous paragraphs. It can be concluded that the hepatic ECM and the ECM in general is a complicated supramolecular assembly of numerous defined macromolecules, each of which is endowed with a specific potential for interactions with one another and with various cell types. This matrix not only adapts rapidly to slight metabolic changes of the cells producing it, but also itself modulates the biochemical and morphologic phenotype of the cells anchored to it. Since mesenchymal cells appear to be the major source of hepatic ECM proteins in health and disease, it follows that the mesenchyme determines to a significant degree the phenotype of liver epithelial cells. Based on the growing knowledge of the hepatic ECM, immunoassays for ECM proteins or peptides in serum may provide information about the dynamics of fibrogenesis or fibrolysis in individual patients on a day to day basis, or permit detection of derangements of the hepatic ECM before they become clinically apparent. The clinical value of such assays is already being studied. Finally, knowing the molecules and the cells involved in ECM pathologic states offers us the tools to develop a specific targeted antifibrogenic therapy.