| Hepatocyte growth factor(HGF) was first identified as the most potent mitogen for hepatocytes in sera from 70% hepatectomized rats by Nakamura et al. HGF is a heterodimer composed of a 69kD a-subunit and a 34kD b-subunit. Recently, HGF has been proved to be the same molecule as scatter factor and tumor cytotoxic factor. Several lines of studies have shown that HGF is the long-sought hepatotrophic factor for liver regeneration. Following the onset of various types of hepatic injuries, HGF messenger RNA expression is rapidly up-regulated in the livers of experimental animals. Serum HGF levels are elevated in patients with various hepatic disorders. Extensive in vivo studies on the efficacy of recombinant HGF on hepatic regeneration revealed that HGF elicits a potent hepatotrophic action. HGF strongly stimulates DNA synthesis of hepatocytes in damaged livers, caused by partial hepatectomy or induced by carbon tetrachloride (CC14) administration. Likewise, HGF suppresses the onset of severe hepatic injuries or maintains the integrity of hepatocytes in the livers of mice with cholestasis induced by a -naphthyl-isothiocyanate; this means that HGF mayhave potent cytoprotective or anti-hepatitis actions, as well as mitogenic action for hepatocytes in vivo.HGF is a kringle-containing polypeptide growth factor that preferentially targets a wide variety of epithelial and endothelial cells, as well as mature hepatocyte. HGF is expressed in mesenchymal or stromal cells and acts as a mesenchymal- (or stromal-) derived paracrine factor for neighboring parenchymal cells. In the liver, HGF is synthesized by nonparenchymal cells and targets both parenchymal hepatocytes and bile duct epithelial cells. In addition to mitogenic activity, HGF enhances the motility of various types of cultured cells as demonstrated by "scatter factor". HGF also plays the role of an epithelial morphogen as it induces branching morphogenesis of renal epithelial cells or nonparenchymal epithelial liver cells in collagen gels. The signal-transducing receptor for HGF is c-met protooncogene product of transmembrane tyrosine kinase.Acute liver failure (ALF) is uncommon but not rare; approximately 200 cases occur annually in the United States, with a mortality approaching 80 percent. Few conditions in medicine are more dramatic or more devastating than ALF. Severe liver-cell dysfunction strikes previously well people suddenly, and many of them die. ALF embraces a number of conditions whose common thread is severe injury of hepatocytes or massive necrosis. Loss of hepatocyte function sets in motion a multiorgan response, and death may occur even when the liver has begun to recover. Hepatic encephalopathy and coagulopathy in the setting of an acute hepatic disease define ALF. The term "fulminant hepatic failure" is generally applied to patients in whom hepatic encephalopathy develops within 8 weeks of the onset of illness, whereas "subfulminant hepatic failure" issued to describe a minority of patientsin whom hepatic encephalopathy develops after a10longer illness, up to 26 weeks in duration. ALF is used as the most suitable umbrella term, since it encompasses all these clinical presentations.On the basis of hepatotrophic and biological activities of HGF to reconstruct tissue structures, as well as its preferential target cell specificity, we asked if HGF might be of potential benefit in treating subjects with acute liver failure. As a result of this study, we now report evidence that exogenously injected recombinant HGF prevents in rats the progress of acute liver failure in experimental models.1. Using technique of recombinant DNA, the eukaryotic expression vectors pEGFP-HGF was successful construted. It contained the full-length human HGF cDNA (2.3kb).2. Hepatocyte cell QZG was transfected with pEGFP mediated by lipofect-AMINE. After G418 selection, we obtained successfully transcripted HGF gene of cells. We named it QZG/pEGFP-HGF. The change of the proliferation behaviors was investigated in QZG/pEGFP-HGF. Compared wit...
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