Up-regulated expression of HGF in rat liver cells after experimental endotoxemia: A potential pathway for enhancement of liver regeneration

A lipopolysaccharide (LPS)-induced inflammation prior to an hepatic resecti on has been shown to enhance liver regeneration in rat. The aim of the pres ent study was to investigate the expression of hepatocyte growth factor (HG F) and its c-Met receptor under such experimental conditions. Animals were submitted to a two-third hepatectomy or a LPS challenge carried out 12 h pr ior to resection. Non parenchymal and parenchymal cells were isolated from livers obtained at various times post-hepatectomy. Quantitative RT-PCR for HGF and c-Met mRNAs were performed from total liver or purified cell fracti ons and HGF mRNA was also analyzed by in situ RT-PCR on liver sections. A L PS challenge alone induced a marked up-regulation of HGF mRNA level in whol e liver and isolated hepatocytes. Furthermore, when partial hepatectomy (PH ) was preceded by a LPS challenge, an increase of HGF mRNA level was seen i n whole liver and contrasted with a decreased level in non parenchymal cell s. These results were confirmed by in situ RT-PCR. In isolated hepatocytes from endotoxemic rats, the mRNA level for the LPS-specific membranous recep tor mCD14 was markedly up-regulated and even more so when LPS was followed by PH. Moreover, a TNF alpha challenge alone induced an up-regulation of HG F mRNA in hepatocytes and a down-regulation in non parenchymal cells (NPCs) . Overall, when a LPS challenge is given prior to PH the major source of he patic HGF appears to be the hepatocyte itself rather than NPCs. An autocrin e HGF/c-Met loop which promotes the proliferative potential of the hepatic parenchymal cell and participates in liver regeneration is postulated.