HEPATOCYTE GROWTH-FACTOR STIMULATES LIVER-REGENERATION AND ELEVATES BLOOD PROTEIN LEVEL IN NORMAL AND PARTIALLY HEPATECTOMIZED RATS

The effects of recombinant human hepatocyte growth factor (HGF) on liv er growth and function of normal and partially hepatectomized rats hav e been examined, HGF was continuously administered into the jugular ve in because it was rapidly eliminated from the plasma (t(1/2)alpha; sim ilar to 4.5 min) and degraded. In normal rats, the labeling index of h epatocytes was increased about 6 times by the administration of HGF. H GF also decreased the prothrombin time and increased the hepaplastin a nd serum albumin content. In 70%-hepatectomized rats, HGF stimulated l iver regeneration and increased the level of blood proteins such as he paplastin in a dose-dependent manner. The stimulation of serum protein level seemed to result from not only the increase of hepatic cell num ber but also the direct effect of HGF on the protein production in hep atocytes, because HGF rapidly enhanced the protein synthesis prior to the increase of cell number and increased the mRNA content of albumin in the liver in vivo. In addition, a combination of heparin with HGF f urther accelerated the effects of HGF described above, possibly due to the decrease of HGF clearance. These findings suggest that HGF accele rates both the hepatic regeneration and function in vivo, and that rhH GF is clinically expected to be a potent therapeutic agent in hepatect omy and liver injury.