Biosynthesis and degradation of hyaluronan by nonparenchymal liver cells during liver regeneration

Hepatic stellate cells (HSC) and endothelial cells of the liver sinusoids synthesize and degrade hyaluronan, respectively. The roles of these cell types in the biosynthesis and degradation of hyaluronan were studied during regeneration following partial hepatectomy. Pure cultures of HSC and liver endothelial cells (LEC) were obtained from regenerating liver at different stages using a Nycodenz gradient followed by discontinuous Percoll gradient. The HSC that established 3 or 4 days after partial hepatectomy synthesized large amounts of hyaluronan when cultured in the presence of fetal calf serum (FCS) or platelet-derived growth factor B-chain homodimer (PDGF)-BB. These cells, as well as LEG, expressed active PDGF beta-receptors. Furthermore, the ability of LEC to degrade hyaluronan was decreased at early stages of Liver regeneration. The increased synthesis of hyaluronan by HSC and the failure of LEC to catabolize the polysaccharide resulted in elevated hyaluronan concentrations in the blood.