Hepatocyte reprogramming in liver regeneration: Biological mechanisms and applications

Abstract

The liver is one of the few organs that retain the capability to regenerate in adult mammals. This regeneration process is mainly facilitated by the dynamic behavior of hepatocytes, which are the major functional cell type in the liver. In response to liver injury, hepatocytes undergo remarkable alterations, such as reprogramming, wherein they lose their original identity and acquire properties from other cells. This phenomenon of hepatocyte reprogramming, coupled with hepatocyte expansion, plays a central role in liver regeneration, and its underlying mechanisms are complex and multifaceted. Understanding the fate of reprogrammed hepatocytes and the mechanisms of their conversion has significant implications for the development of innovative therapeutics for liver diseases. Herein, we review the plasticity of hepatocytes in response to various forms of liver injuries, with a focus on injury‐induced hepatocyte reprogramming. We provide a comprehensive summary of current knowledge on the molecular and cellular mechanisms governing hepatocyte reprogramming, specifically in the context of liver regeneration, providing insight into potential applications of this process in the treatment of liver disorders, including chronic liver diseases and liver cancer.

Enhancement of adult liver regeneration in mice through the hepsin-mediated epidermal growth factor receptor signaling pathway

“…However, the mechanisms that govern the intricate processes underlying liver regeneration remain incompletely understood. 1 Liver regeneration can be classified into three phases, namely priming, proliferation, and termination. [2][3][4] In the priming stage, hepatocytes are stimulated to enter the G1 phase of the cell cycle under the influence of various cytokines.…”