Expression of hepatocyte growth factor and transforming growth factor beta 1 mRNA in P. acnes and lipopolysaccharide-treated rats.

Hepatocyte growth factor (HGF), a potent hepatocyte mitogen in vitro, triggers hepatocyte regeneration after partial hepatectomy and acute liver cell necrosis induced by chemicals. In contrast, transforming growth factor beta 1 inhibits hepatocyte proliferation in vitro and suppresses liver regeneration in vivo. We assessed the expression of HGF and TGF beta 1 mRNA in an endotoxin-related hepatic cell necrosis model. Intravenous injection of Gram-negative lipopolysaccharide (LPS) into rats previously given heat-killed Propionibacterium acnes induced endotoxin-related hepatic cell necrosis. In this model, serum ALT began to rise to more than 100IU as early as 3 h after LPS injection, reaching 300IU 12h after injection. HGF mRNA levels in the liver did not increase significantly until 5h after LPS injection; at 12h, they had increased about threefold compared with controls. TGF beta 1 mRNA expression increased threefold after P. acnes treatment alone and increased further after LPS injection. In the spleen, HGF mRNA levels increased within 3h, but in the lung no increase in HGF mRNA was observed. Early elevation of liver TGF beta 1 mRNA levels and delayed elevation of HGF mRNA levels, with low expression of HGF in the lung, may play a role in the pathogenesis of endotoxin-related hepatic necrosis.