Connective tissue components of the normal and fibrotic liver. I. Structure, local distribution and metabolism of connective tissue components in the normal liver and changes in chronic liver diseases.

The first part of this review describes the chemistry, the occurrence and the metabolism of extracellular connective tissue components in the liver. The normal liver contains typical connective tissue proteins (collagens, structural glycoproteins and proteoglycans) not only in vessel walls, perivascular areas and in the capsule, but they occur also in small amounts in the parenchyma, mainly in the space of Disse along the sinusoidal walls. The "interstitial" collagens type I and III represent the major amount of collagen in the normal as well as in fibrotic liver, showing a relative increase of type III in fibrosis. Basement membrane collagens type IV and V as well as the cysteine-rich collagenous components "7 S collagen" and "short chain collagen" have been shown to occur in extracts prepared after limited pepsin digestion. In the normal liver, basement membrane collagen can hardly be detected within the parenchyma by immunofluorescence microscopy; increased occurrence, however, can be shown along the sinusoids even in early stages of chronic liver diseases. The glycoprotein fibronectin was shown to be distributed very similarly to collagens type I and III, whereas the basement membrane specific glycoprotein laminin is restricted to vessel walls and the epithelial layer of bile ductuli in the normal liver but is also found in the parenchyma in fibrosis. Occurrence of proteoglycans is increased in fibrosis: a change in the composition of glycosaminoglycans from mainly heparan sulfate in the normal to dermatan- and chondroitin sulfate in the fibrotic liver was observed. It is not yet clear which cell type is mainly responsible for increased connective tissue synthesis in fibrosis. The occurrence of cells resembling smooth muscle cells ("myofibroblasts") in connective tissue septa of fibrotic livers and the fact that similar cells which actively synthesize collagen grow from explants of fibrotic livers may indicate the significance of this cell type in the process of liver fibrosis.