Following hepatectomy, liver "knows" when to start and when to stop growing
, and thereby accurately regulates its mass. Partial hepatectomy triggers h
epatocyte proliferation whereas excessive liver mass (transplant) is regula
ted by apoptosis. Liver regeneration mainly involves the activation of adul
t hepatocytes and possibly of liver precursor ("stem") cells. The multistep
process of liver regeneration comprises at least 2 critical phases: the tr
ansition of the quiescent hepatocyte into the cell cycle (priming) and the
progression beyond the restriction point in the G, phase of the cycle. The
priming phase is characterized by the expression of immediate early genes.
Activation of protooncogenes in the immediate early gene response involves
both transcriptional and post-transcriptional mechanisms. Activation of fou
r transcription factors, NF kappaB, STAT3, AP-1, and C/EBP beta, causes sec
ondary activation of multiple genes and plays an important role in the init
iation of hepatic regeneration. The passage of primed hepatocytes through t
he cell cycle is characterized by the expression of cell. cycle genes and r
equires growth factors. An equilibrium between stimulator and inhibitor gen
es of the cell cycle expressed after hepatectomy, may explain why the liver
regeneration is a tightly regulated growth process. Based on the knowledge
of the regulation of liver regeneration, several practical considerations
and potential therapeutic strategies can be applied in humans with hepatic
dysfunction due to liver resection.