Regulation of Apoptosis-Associated Genes in the Regenerating Liver

ABSTRACT

The ability of the liver to regenerate remains a fascinating response to hepatic injury. Ever since the Greek myth of Prometheus, efforts have been made to unravel the mechanisms involved in liver regeneration. The cellular phenomenon represents an orchestrated response to external stimuli followed by sequential changes in gene expression, cytokine production, and morphologic structure. The most popular experimental model is based on the surgical removal of two-thirds of the liver. The remnant lobes respond to the loss of mass and function with expression of immediate- and delay-early genes which prime the cells for eventual progression through the cell cycle. The molecular events which trigger liver regeneration are now beginning to unfold. However, the control of liver regeneration and the events involved in regulating the three-dimensional growth of the organ remain poorly defined. It now appears that apoptosis probably plays a key role in fine tuning the regenerative response. The list of apoptosisrelated gene products seems to grow regularly and includes both pro- and antiapoptotic factors. It is noteworthy that many of these genes are critical mediators of both apoptosis and cell replication. The factors involved in predicting which pathway they chose provide the basis for uncovering the secrets of organ growth-be it by life or by death.

KEY WORDS

cell cycle - hepatocyte - proto-oncogene - retinoblastoma - signal transduction