Ductular reactions in the liver regeneration process with local inflammation after physical partial hepatectomy.
Partial hepatectomy models in mice have been widely used for liver regeneration studies. A typical procedure removes ~2/3 of the liver by lobular ligation without tissue dissection. However, hepatectomy in humans involves physical damage (ie, physical partial hepatectomy, PPHx). Therefore, the liver regeneration process after PPHx should involve reactions to acute local injury followed by systematic remodeling. To clarify the liver regeneration process after PPHx, we used a murine liver injury model that mimics the actual human surgical procedure. A 20-30% PPHx was performed by transection of the left lobe of the liver using an ultrasonically activated scalpel in mice. Gene expression and morphological characteristics were analyzed during the liver regeneration process. Liver weight continuously increased by hypertrophic reaction of hepatocytes, whereas Ki67 staining showed hepatocyte proliferation. At the transected border, emergence of ductular reactions, a representative process of hepatic tissue remodeling that contain liver stem/progenitor cells, were observed. Gene expression of the transected border and non-damaged lobes revealed that inflammatory cytokine- and extracellular matrix-associated genes were significantly upregulated at the transected border. Our PPHx model triggered local extracellular matrix remodeling that resulted in ductular reactions. These processes occurred during the tissue repair process in local inflammatory responses as well as compensatory hepatocyte hypertrophy of the entire liver. These findings may provide insight for elucidating the mechanism of tissue repair and regeneration of the liver after PPHx.
Molecular Therapeutics Laboratory, Department of Surgery, School of Medicine, Iwate Medical University, Morioka, Japan.|Division of Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka, Japan.
Yuji
Y
Suzuki
Molecular Therapeutics Laboratory, Department of Surgery, School of Medicine, Iwate Medical University, Morioka, Japan.
Hirokatsu
H
Katagiri
Division of Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka, Japan.
Ting
T
Wang
Division of Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka, Japan.
Keisuke
K
Kakisaka
Molecular Therapeutics Laboratory, Department of Surgery, School of Medicine, Iwate Medical University, Morioka, Japan.|Institute of Biomedical Sciences, Iwate Medical University, Yahaba, Japan.
Kohei
K
Kume
Molecular Therapeutics Laboratory, Department of Surgery, School of Medicine, Iwate Medical University, Morioka, Japan.|Institute of Biomedical Sciences, Iwate Medical University, Yahaba, Japan.
Satoshi S
SS
Nishizuka
Division of Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka, Japan.
Yasuhiro
Y
Takikawa
D000199:Actins / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation; D005109:Extracellular Matrix / Q000502:physiology; D005260:Female; D020869:Gene Expression Profiling; D006498:Hepatectomy; D055166:Hepatic Stellate Cells / Q000378:metabolism; D022781:Hepatocytes / Q000502:physiology; D006984:Hypertrophy; D051550:I-kappa B Kinase / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000276:immunology / Q000473:pathology*; D008115:Liver Regeneration; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D016328:NF-kappa B / Q000378:metabolism; D013234:Stem Cells / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000199:Actins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C544013:alpha-smooth muscle actin, mouse; D051550:I-kappa B Kinase; D020782:Matrix Metalloproteinases