Related Experiment Video
Updated: Jun 6, 2026
Extended 78% Hepatectomy in a Mouse Surgical Model
Published on: May 24, 2024
Vitamin D3 up-regulated protein 1 deficiency accelerates liver regeneration after partial hepatectomy in mice
Hyo-Jung Kwon1, Young-Suk Won, Yeo-Dae Yoon
1Biomedical Mouse Resource Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk, Republic of Korea.
Background & Aims:
Liver regeneration is a complicated process involving a variety of interacting factors. Vitamin D3 up-regulated protein 1 (VDUP1) is a potent growth suppressor that, upon over-expression, inhibits tumor cell proliferation and cell-cycle progression. Here, we investigated the function of VDUP1 in liver regeneration following hepatectomy in mice.
Methods:
Liver regeneration after 70% partial hepatectomy (PH) was compared in VDUP1 knockout (KO) and wild-type (WT) mice, and the activities of proliferative- and cell-cycle-related signaling pathways were measured.
Results:
Compared with WT mice, liver recovery was significantly accelerated in VDUP1 KO mice during the first day after PH, in association with increased DNA synthesis. Consistent with this observation, the expression levels of key cell-cycle regulatory proteins, including cyclin D, cyclin E, cyclin-dependent kinase 4 (CDK4), p21, and p27, were markedly altered in the livers of VDUP1 KO mice. Induction of growth factors and activation of proliferative signaling pathway components including extracellular signal-regulated kinase 1/2 (ERK1/2), Akt, glycogen synthase kinase 3β (GSK3β), mammalian target of rapamycin (mTOR), and p70S6 kinase (p70(S6K)), occurred much earlier and to a greater extent in VDUP1 KO mouse livers. In addition, primary hepatocytes isolated from VDUP1 KO mice displayed increased activation of ERK1/2 and Akt in response to HGF and TGF-α.
Conclusions:
Our results reveal an important role for VDUP1 in the regulation of proliferative signaling during liver regeneration. Altered activation of genes involved in ERK1/2 and Akt signaling pathways may explain the accelerated growth responses seen in VDUP1 KO mice.
Insights
Vitamin D3 up-regulated protein 1 (VDUP1) suppresses liver growth. Its absence accelerates liver regeneration after partial hepatectomy by enhancing cell-cycle progression and proliferative signaling pathways in mice.
Area of Science:
- Hepatology and regenerative medicine.
- Molecular biology and cell signaling.
Background:
- Liver regeneration is a complex biological process critical for restoring liver mass after injury.
- Vitamin D3 up-regulated protein 1 (VDUP1) is identified as a potent suppressor of cell proliferation and cell-cycle progression.
- The precise role of VDUP1 in the context of liver regeneration remains largely unexplored.
Purpose of the Study:
- To elucidate the functional role of VDUP1 in the process of liver regeneration following surgical removal of liver tissue (hepatectomy).
- To investigate the impact of VDUP1 deficiency on the kinetics and molecular mechanisms governing liver recovery.
Main Methods:
- Comparative analysis of liver regeneration in VDUP1 knockout (KO) and wild-type (WT) mice after 70% partial hepatectomy (PH).
- Assessment of DNA synthesis and expression levels of key cell-cycle regulatory proteins.
- Measurement of signaling pathway activities, including extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt pathways.
Main Results:
- VDUP1 KO mice exhibited significantly accelerated liver recovery and increased DNA synthesis within 24 hours post-PH compared to WT mice.
- Marked alterations in cell-cycle proteins (cyclin D, E, CDK4, p21, p27) were observed in VDUP1 KO livers.
- Earlier and enhanced induction of growth factors and activation of proliferative signaling pathways (ERK1/2, Akt, mTOR) were evident in VDUP1 KO mice.
Conclusions:
- VDUP1 plays a significant regulatory role in controlling proliferative signaling during liver regeneration.
- The accelerated liver growth in VDUP1 KO mice is attributed to the enhanced activation of ERK1/2 and Akt signaling pathways.
