The Molecular Biology of Liver Regeneration 
have observed in the liver posthepatectomy, and 
our findings suggest that PHF- 1 could have a role 
as an initiating signal in liver regeneration. 
LRF- 1 (liver regeneration factor) is one of the 
proteins that we have studied that is highly ex- 
pressed in regenerating liver and functions as a 
DNA-binding protein, controlling the expression 
of target genes. It falls into the category of so- 
called leucine zipper proteins, in which a stretch 
of amino acids containing evenly spaced leucine 
residues allows one molecule of LRF- 1 to interact 
with another molecule of LRF-1 or of a related 
protein. LRF-1 activates or inhibits the expression 
of target genes in a singular manner, implying 
that LRP-1 has a unique role in regulating events 
in the regenerative process. As the relative level 
of LRF- 1 complexes increases posthepatectomy, 
activation of the many liver-specific genes oc- 
curs, resulting in maintenance of normal liver 
function and metabolic homeostasis during 
regeneration. 
Another goal of our research (supported in part 
by research funds from other agencies) is to un- 
derstand the involvement of insulin in the regula- 
tion of hepatic growth. It is well known that dia- 
betics have poor healing capacity, and early 
studies have shown that the livers of diabetic ani- 
mals show poor regenerative capacity. Because 
we are studying a liver cell line that is growth- 
regulated by insulin, we have been able to com- 
pare the insulin-regulated growth response in 
these cells with the response during liver regen- 
eration. Differences in expression of more than 
1 0 of the novel genes we have identified suggest 
that insulin, if it is an important growth factor 
during liver regeneration, must act several hours 
after the hepatectomy and is not an initiating fac- 
tor. Additionally, in examining the encoded func- 
tion of several genes that are aberrantly regulated 
in the hepatic cell line, we are learning more 
about the specific signaling pathways involved in 
hepatic growth. 
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