Molecular Mechanisms of Liver Injury and Hepatocarcinogenesis: Focusing on the Role of Stress-Activated MAPK

Figure 3

Current model of the role of stress-activated MAPK and NF-κB in inflammation-mediated hepatocarcinogenesis. In chronic liver injury, hepatitis virus, ROS, toxins, and cytokines kill hepatocytes. JNK promotes cell death, while NF-κB and p38 promote cell survival. Dying hepatocytes activate Kupffer cells via TLR or IL-1R. Activated Kupffer cells secrete cytokines, such as IL-6 and TNFα, through a mechanism mediated by NF-κB and p38. Subsequently, these cytokines induce recruitment of activated inflammatory cells to the liver, which is followed by hepatocyte regeneration. JNK and STAT3 promote cytokine-mediated hepatocyte proliferation. This persistent cycle of necroinflammation and hepatocyte regeneration provides a mitogenic and mutagenic environment, leading to the development of HCC.