Proliferation‑inhibiting pathways in liver regeneration (Review).

Liver regeneration, an orchestrated process, is the primary compensatory mechanism following liver injury caused by various factors. The process of liver regeneration consists of three stages: Initiation, proliferation and termination. Proliferation‑promoting factors, which stimulate the recovery of mitosis in quiescent hepatocytes, are essential in the initiation and proliferation steps of liver regeneration. Proliferation‑promoting factors act as the 'motor' of liver regeneration, whereas proliferation inhibitors arrest cell proliferation when the remnant liver reaches a suitable size. Certain proliferation inhibitors are also expressed and activated in the first two steps of liver regeneration. Anti‑proliferation factors, acting as a 'brake', control the speed of proliferation and determine the terminal point of liver regeneration. Furthermore, anti‑proliferation factors function as a 'steering‑wheel', ensuring that the regeneration process proceeds in the right direction by preventing proliferation in the wrong direction, as occurs in oncogenesis. Therefore, proliferation inhibitors to ensure safe and stable liver regeneration are as important as proliferation‑promoting factors. Cytokines, including transforming growth factor‑β and interleukin‑1, and tumor suppressor genes, including p53 and p21, are important members of the proliferation inhibitor family in liver regeneration. Certain anti‑proliferation factors are involved in the process of gene expression and protein modification. The suppression of liver regeneration led by metabolism, hormone activity and pathological performance have been reviewed previously. However, less is known regarding the proliferation inhibitors of liver regeneration and further investigations are required. Detailed information regarding the majority of known anti‑proliferation signaling pathways also remains fragmented. The present review aimed to understand the signalling pathways that inhbit proliferation in the process of liver regeneration.