Collagen III regulates the termination of liver regeneration by suppressing hepatocyte proliferation and promoting functional recovery

Termination of liver regeneration is important for restoring hepatic function after partial hepatectomy (PHx); however, its regulatory mechanisms remain poorly understood. The present study aimed to investigate the role of collagen III (col3) in terminating liver regeneration and its interaction with the β‑catenin signaling pathway. Initially, a 2/3 PHx mouse model was established, and col3 expression dynamics were examined via immunofluorescence and reverse transcription‑quantitative PCR. Collagenase III, also known as matrix metalloproteinase‑13, was used to degrade col3 during the termination phase of liver regeneration, and the resulting effects on hepatocyte proliferation, β‑catenin signaling and liver function were assessed. Methyl‑sulfonyl AB (MSAB), a β‑catenin inhibitor, was used to explore pathway involvement. The present study demonstrated that col3 expression in the parenchymal areas of the liver was decreased during the proliferation phase and increased during the termination phase. Collagenase‑induced col3 degradation enhanced hepatocyte proliferation, delayed regenerative termination, activated β‑catenin signaling, and impaired hepatocyte differentiation and liver function. Administration of MSAB rescued these effects, partially restoring termination and function. In conclusion, col3 may regulate the termination of liver regeneration by suppressing hepatocyte proliferation and promoting functional recovery. These findings provide new insights into collagen‑induced regulation of liver regeneration and potential therapeutic targets for optimizing hepatic recovery.