Rapid induction of mRNAs for liver regeneration factor and insulin-like growth factor binding protein-1 in primary cultures of rat hepatocytes by hepatocyte growth factor and epidermal growth factor.
Liver regeneration factor belongs to the leucine-zipper family of transcription factors. It was originally cloned and characterized through differential screening of a regenerating rat liver cDNA library. The mRNA for liver regeneration factor-1 is barely detectable in normal rat liver but is dramatically induced after two-thirds hepatectomy, with a peak 1 to 3 hr after surgery. The nature of the signaling molecule(s) for this rapid induction is not known. It has been suggested that the liver regeneration factor-1 protein product, through complex interactions with other transcription factors such as c-Jun and Jun-B, controls expression of genes that are required during the G1 phase of hepatic growth. Hepatocyte growth factor has been shown to be the most potent mitogen for hepatocytes in vitro and in vivo. Plasma levels of hepatocyte growth factor rapidly (within 30 min) increase after loss of hepatic parenchyma induced by partial hepatectomy or carbon tetrachloride treatment. It has been postulated that hepatocyte growth factor plays a crucial role in stimulating the hepatocyte to enter the cell cycle. In this communication, we report that addition of pure hepatocyte growth factor to primary cultures of rat hepatocytes in the absence of serum and insulin results in rapid and transient induction of liver regeneration factor-1 mRNA (more than 20-fold) with a peak of expression 1 hr after treatment. The levels of jun-B and c-fos mRNAs, which are also known to be induced during the early hours of liver regeneration, were also increased after treatment of isolated hepatocytes with hepatocyte growth factor.(ABSTRACT TRUNCATED AT 250 WORDS)
Weir
E
E
Department of Pathology, University of Pittsburgh, School of Medicine, Pennsylvania 15261.
Chen
Q
Q
DeFrances
M C
MC
Bell
A
A
Taub
R
R
Zarnegar
R
R
D051700:Activating Transcription Factor 3; D000818:Animals; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D016762:Genes, fos; D016758:Genes, jun; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D016350:Leucine Zippers / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D008115:Liver Regeneration; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D015854:Up-Regulation
D051700:Activating Transcription Factor 3; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D018970:Insulin-Like Growth Factor Binding Protein 1; D012333:RNA, Messenger; C068616:liver regeneration factor 1; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor; D007334:Insulin-Like Growth Factor I