Impaired liver regeneration with humoral and genetic disturbances in urinary trypsin inhibitor-deficient mice
Takayuki Nobuoka
Department of Surgery I, Sapporo Medical University Hospital, Sapporo Medical University School of Medicine, Sapporo, Japan
Search for more papers by this authorToru Mizuguchi
Department of Surgery I, Sapporo Medical University Hospital, Sapporo Medical University School of Medicine, Sapporo, Japan
Search for more papers by this authorHideki Oshima
Department of Surgery I, Sapporo Medical University Hospital, Sapporo Medical University School of Medicine, Sapporo, Japan
Search for more papers by this authorToshihito Shibata
Department of Surgery I, Sapporo Medical University Hospital, Sapporo Medical University School of Medicine, Sapporo, Japan
Search for more papers by this authorShinsuke Kaji
Department of Surgery I, Sapporo Medical University Hospital, Sapporo Medical University School of Medicine, Sapporo, Japan
Search for more papers by this authorMinoru Nagayama
Department of Surgery I, Sapporo Medical University Hospital, Sapporo Medical University School of Medicine, Sapporo, Japan
Search for more papers by this authorMakoto Meguro
Department of Surgery I, Sapporo Medical University Hospital, Sapporo Medical University School of Medicine, Sapporo, Japan
Search for more papers by this authorToshihiro Mitaka
Department of Pathophysiology, Cancer Research Institute, Sapporo Medical University School of Medicine, Sapporo, Japan
Search for more papers by this authorKoichi Hirata
Department of Surgery I, Sapporo Medical University Hospital, Sapporo Medical University School of Medicine, Sapporo, Japan
Search for more papers by this authorTakayuki Nobuoka
Department of Surgery I, Sapporo Medical University Hospital, Sapporo Medical University School of Medicine, Sapporo, Japan
Search for more papers by this authorToru Mizuguchi
Department of Surgery I, Sapporo Medical University Hospital, Sapporo Medical University School of Medicine, Sapporo, Japan
Search for more papers by this authorHideki Oshima
Department of Surgery I, Sapporo Medical University Hospital, Sapporo Medical University School of Medicine, Sapporo, Japan
Search for more papers by this authorToshihito Shibata
Department of Surgery I, Sapporo Medical University Hospital, Sapporo Medical University School of Medicine, Sapporo, Japan
Search for more papers by this authorShinsuke Kaji
Department of Surgery I, Sapporo Medical University Hospital, Sapporo Medical University School of Medicine, Sapporo, Japan
Search for more papers by this authorMinoru Nagayama
Department of Surgery I, Sapporo Medical University Hospital, Sapporo Medical University School of Medicine, Sapporo, Japan
Search for more papers by this authorMakoto Meguro
Department of Surgery I, Sapporo Medical University Hospital, Sapporo Medical University School of Medicine, Sapporo, Japan
Search for more papers by this authorToshihiro Mitaka
Department of Pathophysiology, Cancer Research Institute, Sapporo Medical University School of Medicine, Sapporo, Japan
Search for more papers by this authorKoichi Hirata
Department of Surgery I, Sapporo Medical University Hospital, Sapporo Medical University School of Medicine, Sapporo, Japan
Search for more papers by this authorAbstract
Background/Aims: Urinary trypsin inhibitor (UTI) is an innate anti-inflammatory regulator. It can block the release of inflammatory factors, prevent the cascade reaction of cytokines and inhibit excessive activation of leukocytes. Liver regeneration (LR) is a dynamic molecular phenomenon without inflammation. Many cytokines, including tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6), have been implicated in regulating LR. However, the role of UTI in LR is totally unknown. The aim of this study was to elucidate the role of UTI in LR using genetically UTI-deficient mice.
Methods: We performed 68% hepatectomy, comparing UTI (−/−) and UTI (+/+) mice. Recovery of liver weight was recorded and we calculated labelling indices after 5-bromo-2′-deoxyuridine (BrdU) immunohistochemistry. A DNA microarray was used to examine gene expression followed by real-time polymerase chain reaction. Serum IL-6, IL-10, monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1β (MIP-1β) were measured.
Results: LR in UTI (−/−) mice was delayed at 36 h after hepatectomy, at which time the DNA profile was different. One hundred and fourteen genes were upregulated and 100 genes were downregulated in UTI (−/−) mice at 36 h after hepatectomy among the 21, 977 mRNAs examined. Furthermore, serum IL-6, IL-10, MCP-1 and MIP-1β levels at 36 h after hepatectomy in the UTI (−/−) mice were significantly higher than in the UTI (+/+) mice.
Conclusion: UTI appears to important cytokine and chemokine regulation in normal liver regeneration.
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