Mechanism of impaired regeneration of fatty liver in mouse partial hepatectomy model
Hiroshi Murata
Department of Gastroenterological Surgery, Transplant and Surgical Oncology, and
Search for more papers by this authorTakahito Yagi
Department of Gastroenterological Surgery, Transplant and Surgical Oncology, and
Search for more papers by this authorHiromi Iwagaki
Department of Gastroenterological Surgery, Transplant and Surgical Oncology, and
Search for more papers by this authorTetsuya Ogino
Department of Pathology, Okayama University Graduate School of Medicine and Dentistry, Shikata, Okayama, and
Search for more papers by this authorHiroshi Sadamori
Department of Gastroenterological Surgery, Transplant and Surgical Oncology, and
Search for more papers by this authorHiroyoshi Matsukawa
Department of Gastroenterological Surgery, Transplant and Surgical Oncology, and
Search for more papers by this authorYuzoh Umeda
Department of Gastroenterological Surgery, Transplant and Surgical Oncology, and
Search for more papers by this authorSanae Haga
Department of Surgery, School of Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Japan
Search for more papers by this authorNoriaki Takaka
Department of Gastroenterological Surgery, Transplant and Surgical Oncology, and
Search for more papers by this authorCorresponding Author
Michitaka Ozaki
Department of Surgery, School of Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Japan
Dr Michitaka Ozaki, Division of Organ Transplantation and Regenerative Medicine, Department of Surgery, School of Medicine, Hokkaido University Graduate School of Medicine, N-15, W-7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan. Email: [email protected]Search for more papers by this authorHiroshi Murata
Department of Gastroenterological Surgery, Transplant and Surgical Oncology, and
Search for more papers by this authorTakahito Yagi
Department of Gastroenterological Surgery, Transplant and Surgical Oncology, and
Search for more papers by this authorHiromi Iwagaki
Department of Gastroenterological Surgery, Transplant and Surgical Oncology, and
Search for more papers by this authorTetsuya Ogino
Department of Pathology, Okayama University Graduate School of Medicine and Dentistry, Shikata, Okayama, and
Search for more papers by this authorHiroshi Sadamori
Department of Gastroenterological Surgery, Transplant and Surgical Oncology, and
Search for more papers by this authorHiroyoshi Matsukawa
Department of Gastroenterological Surgery, Transplant and Surgical Oncology, and
Search for more papers by this authorYuzoh Umeda
Department of Gastroenterological Surgery, Transplant and Surgical Oncology, and
Search for more papers by this authorSanae Haga
Department of Surgery, School of Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Japan
Search for more papers by this authorNoriaki Takaka
Department of Gastroenterological Surgery, Transplant and Surgical Oncology, and
Search for more papers by this authorCorresponding Author
Michitaka Ozaki
Department of Surgery, School of Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Japan
Dr Michitaka Ozaki, Division of Organ Transplantation and Regenerative Medicine, Department of Surgery, School of Medicine, Hokkaido University Graduate School of Medicine, N-15, W-7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan. Email: [email protected]Search for more papers by this authorAbstract
Background and Aim: The mechanism of injury in steatotic liver under pathological conditions been extensively examined. However, the mechanism of an impaired regeneration is still not well understood. The aim of this study was to analyze the mechanism of impaired regeneration of steatotic liver after partial hepatectomy (PH).
Methods: db/db fatty mice and lean littermates were used for the experiments. Following 70% PH, the survival rate and recovery of liver mass were examined. Liver tissue was histologically examined and analyzed by western blotting and RT-PCR.
Results: Of 35 db/db mice, 25 died within 48 h of PH, while all of the control mice survived. Liver regeneration of surviving db/db mice was largely impaired. In db/db mice, mitosis of hepatocytes after PH was disturbed, even though proliferating cell nuclear antigen (PCNA) expression (G1 to S phase marker) in hepatocytes was equally observed in both mice groups. Interestingly, phosphorylation of Cdc2 in db/db mice was suppressed by reduced expression of Wee1 and Myt1, which phosphorylate Cdc2 in S to G2 phase.
Conclusions: In steatotic liver, cell-cycle-related proliferative disorders occurred at mid-S phase after PCNA expression. Reduced expression of Wee1 and Myt1 kinases may therefore maintain Cdc2 in an unphosphorylated state and block cell cycle progression in mid-S phase. These kinases may be critical factors involved in the impaired liver regeneration in fatty liver.
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