The second layer of defense lies in the reserve progenitor cell population, which is also a quiescent compartment in the click here liver, but is activated when injury is severe, or when the mature hepatocytes can no longer regenerate the liver due to senescence

or arrest. Regeneration of the liver after resection is actually compensatory hyperplasia rather than a true restoration of the liver’s original gross anatomy and architecture.1,2 A particularly fascinating point about this process is that the degree of hyperplasia is precisely controlled by the metabolic needs of the organism, such that the process stops once an appropriate liver to body weight ratio is achieved. Two-thirds partial hepatectomy

(PH) in rodents has been used extensively to study molecular and cellular mechanisms behind liver regeneration, with initial physiologic Selleck MG-132 principles outlined in rats through the pioneering work of Nancy Bucher.5–7 Later, the advent of genetically modified mice allowed the study of various specific molecules and dissection of pathways implicated in regeneration. More recently, studies of global gene expression profiling have returned our thoughts to the “big picture”, as there are clearly multiple overlapping redundant pathways working in concert to achieve this impressive physiologic accomplishment. PH is reproducible and leads medchemexpress to a proliferative stimulus that is initiated by an inflammatory stimulus, in the absence of significant cell death. Regeneration of the liver is critical to the survival of mammals and is therefore evolutionarily conserved. Thus, pathways leading to its completion are (with few exceptions) redundant. The phenotype of most genetically modified mouse models studied using the PH model thus consists of a delay rather than a complete abrogation of regeneration. Given the extent of cell proliferation needed to restore original mass after 2/3 PH, it is intuitive that virtually all cellular machinery be activated during regeneration, and that

this could realistically entail hundreds of pathways. It is proposed that there is an initial activation of the cytokine cascade in Kupffer cells, which then stimulates growth factor and metabolic pathways in hepatocytes. Other non-parenchymal cells (stellate cells, vascular and biliary endothelial cells) proliferate after hepatocytes, presumably responding to yet another set of signals. A great deal of recent work has focused on how pattern recognition receptors and a variety of inflammatory molecules are activated and initiate the cytokine signaling cascade after PH. As they have been extensively discussed elsewhere,2 we will not go into great detail about these pathways in this review.