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Cited by 16Liver physiology and pathologyOrgan Transplantation Techniques and OutcomesTissue Engineering and Regenerative Medicine

Ductular reactions in the liver regeneration process with local inflammation after physical partial hepatectomy

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Suzuki, Yuji, Katagiri, Hirokatsu, Wang, Ting, Kakisaka, Keisuke, Kume, Kohei, Nishizuka, Satoshi S, Takikawa, Yasuhiro·2016·Laboratory Investigation
DOI 10.1038/labinvest.2016.97
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Abstract

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.

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  • Liver resection almost always results in mechanical liver tissue damage, including deterioration of extracellular matrix and inflammatory response, and ductular reactions associated with local inflammation and extracellular matrix remodeling in the dissection area are often revealed.

    “In clinical surgery, when the liver resection almost always results in mechanical liver tissue damage, including deuteriation of ECM and inflammatory response[2], the DR associated with local inflammation and ECM remodeling in the dissection area, are often revealed[84].”

    From Liver regeneration after partial hepatectomy: Triggers and mechanisms (2025) · cites this paper as [84]

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Cited by

Sorted by citations

Authors
Suzuki, Y., Katagiri, H., Wang, T., Kakisaka, K., Kume, K., Nishizuka, S. S., & Takikawa, Y.
Affiliations
Iwate Medical University (JP)
Corresponding author
Nishizuka, Satoshi S
ORCID
Venue
Laboratory Investigation
Publisher
Elsevier BV
Published
2016-11
Volume
96
Issue
11
Pages
1211-1222
ISSN
0023-6837 (ISSN-L)
DOI
10.1038/labinvest.2016.97
OpenAlex
W2519504486
Cited by
16
References
2
Citations by year
2025: 2 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 3
FWCI
1.44
Type
journal article
Language
en
Open access
Licence
Locations
  • Laboratory Investigation (publishedVersion)
  • PubMed (publishedVersion)
Funders
Japan Society for the Promotion of Science (16K09370)
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords
ductular reaction, liver regeneration, hepatocyte hypertrophy, hepatocyte proliferation, liver progenitor cells, extracellular matrix remodeling, inflammatory cytokines, tissue repair, liver injury, harmonic scalpel
MeSH terms
Actins, Animals, Extracellular Matrix, Female, Hepatectomy, Hypertrophy, Liver, Liver Regeneration, Mice, Inbred C57BL, Stem Cells, Tumor Necrosis Factor-alpha, NF-kappa B, Matrix Metalloproteinases, Gene Expression Profiling, Hepatocytes, Models, Animal, Cell Proliferation, I-kappa B Kinase, Hepatic Stellate Cells

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