Unraveling the cellular mechanisms of liver regeneration, how does Transglutaminase 2 influence the repair process following toxic injury? This research investigates the role of Tgm2 in ductular reaction (DR), a crucial process for liver regeneration during cholestatic liver injury. The study uses Tgm2-knockout mice and three-dimensional (3D) collagen gel culture of mouse hepatocytes to demonstrate how Tgm2 signalling is involved in DR to remodel intrahepatic cholangiocytes. The study finds that the deletion of Tgm2 adversely affected the functionality and maturity of the proliferative cholangiocytes in DR, thus leading to more severe cholestasis during DDC-induced liver injury. Tgm2 hepatocytes played a crucial role in the regulation of DR through metaplasia. The authors unveil that Tgm2 regulated H3K4me3Q5ser via serotonin to promote BMP signalling activation to participate in DR. The research further demonstrates that the activation or inhibition of BMP signalling could promote or suppress the development and maturation of cholangiocytes in DDC-induced DR. Tgm2 was vital for the development of cholangiocytes in vitro. In conclusion, the findings uncover a considerable role of BMP signalling in controlling metaplasia of Tgm2 hepatocytes in DR and reveal the phenotypic plasticity of mature hepatocytes. It is vital for the development of cholangiocytes in vitro and could promote or suppress the development and maturation of cholangiocytes in DDC-induced DR. These results provides insight into Tgm2 signaling and helps expand understanding of liver repair following toxic injury.
Published in Cell Proliferation, this research aligns with the journal's focus on the mechanisms of cell growth and division, particularly in the context of disease. By investigating the role of Tgm2 in liver regeneration and ductular reaction, the paper contributes to the understanding of cellular processes involved in tissue repair and remodeling. This study is relevant to researchers in cell biology, molecular biology, and liver disease.