Identification and change in the receptor for hepatocyte growth factor in rat liver after partial hepatectomy or induced hepatitis.
Specific binding of 125I-labeled human recombinant HGF to the primary cultured rat hepatocytes or liver plasma membranes was observed to be temperature- and time-dependent. Scatchard analysis indicated the presence of a single class of high affinity receptors with a dissociation constant (Kd) of 24-32 pM, a value in good accord with half maximum dose for HGF activity and a receptor density of about 500-600 sites/cell. Affinity cross-linking of the receptor with 125I-HGF revealed the HGF receptor in rat liver membranes to be a polypeptide of Mr approximately 220,000. After partial hepatectomy, specific binding of 125I-HGF to the membranes of residual livers decreased by 60-70% between 3 and 6 h, and was scanty at 12 h after hepatectomy. After one week, the binding was recovered to the 1.7 fold level in the untreated rat liver. This rapid down-regulation of HGF receptors was also observed in plasma membranes of rat livers in the presence of hepatitis induced by CCl4. We propose that HGF which can be immediately supplied to the liver after hepatic injury will function as a trigger for regeneration of this organ.
Higuchi
O
O
Department of Biology, Faculty of Science, Kyushu University, Fukuoka, Japan.
Nakamura
T
T
D000818:Animals; D002251:Carbon Tetrachloride; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D015536:Down-Regulation; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism*; D006498:Hepatectomy; D017228:Hepatocyte Growth Factor; D006801:Humans; D008099:Liver / Q000737:chemistry* / Q000502:physiology; D008115:Liver Regeneration; D008297:Male; D008970:Molecular Weight; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D016211:Transforming Growth Factor alpha / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
D003432:Cross-Linking Reagents; D006133:Growth Substances; D011994:Recombinant Proteins; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor; D004247:DNA; D002251:Carbon Tetrachloride