Liver Regeneration: Analysis of the Main Relevant Signaling Molecules

Abstract

Liver regeneration is a highly organized tissue regrowth process and is the most important reaction of the liver to injury. The overall process of liver regeneration includes three phases: priming stage, proliferative phase, and termination phase. The initial step aims to induce hepatocytes to be sensitive to growth factors with the aid of some cytokines, including TNF-α and IL-6. The proliferation phase promotes hepatocytes to re-enter G1 with the stimulation of growth factors. While during the termination stage, hepatocytes will discontinue to proliferate to maintain normal liver mass and function. Except for cytokine- and growth factor-mediated pathways involved in regulating liver regeneration, new substances and technologies emerge to influence the regenerative process. Here, we reviewed novel and important signaling molecules involved in the process of liver regeneration to provide a cue for further research.

Figure 1

The outline of liver regeneration process.

Figure 2

The production of TNF-α and IL-6 in Kupffer cell through NF-κB signaling in the early phase of liver regeneration.

Figure 3

Growth factors, along with some cytokines, guide the progression of liver regeneration through expression of some cell cycle-related proteins mainly by PI3K/AKT, wnt-independent/β-catenin, Ras/MAPK, and JAK/STAT signaling pathways.