Differential expression of lutheran/BCAM regulates biliary tissue remodeling in ductular reaction during liver regeneration

Yasushi Miura, Satoshi Matsui, Naoko Miyata, Kenichi Harada, Yamato Kikkawa, Masaki Ohmuraya, Kimi Araki, Shinya Tsurusaki, Hitoshi Okochi, Nobuhito Goda, Atsushi Miyajima, Minoru Tanaka

    Research output: Contribution to journalArticle

    1 Citation (Scopus)

    Abstract

    Under chronic or severe liver injury, liver progenitor cells (LPCs) of biliary origin are known to expand and contribute to the regeneration of hepatocytes and cholangiocytes. This regeneration process is called ductular reaction (DR), which is accompanied by dynamic remodeling of biliary tissue. Although the DR shows apparently distinct mode of biliary extension depending on the type of liver injury, the key regulatory mechanism remains poorly understood. Here, we show that Lutheran (Lu)/Basal cell adhesion molecule (BCAM) regulates the morphogenesis of DR depending on liver disease models. Lu+ and Lu- 55 biliary cells isolated from injured liver exhibit opposite phenotypes in cell motility and duct formation capacities in vitro. By overexpression of Lu, Lu- biliary cells acquire the phenotype of Lu+ 57 biliary cells. Lu-deficient mice showed severe defects in DR. Our findings reveal a critical role of Lu in the control of phenotypic heterogeneity of DR in distinct liver disease models.

    Original languageEnglish
    Article numbere36572
    JournaleLife
    Volume7
    DOIs
    Publication statusPublished - 2018 Jul 30

    Fingerprint

    Liver Regeneration
    Cell Adhesion Molecules
    Liver
    Tissue
    Liver Diseases
    Regeneration
    Phenotype
    Wounds and Injuries
    Morphogenesis
    Cell Movement
    Hepatocytes
    Stem Cells
    Ducts
    Defects

    Keywords

    • Ductular reaction
    • Integrin β1
    • Laminin
    • Oval cell
    • Regeneration

    ASJC Scopus subject areas

    • Neuroscience(all)
    • Biochemistry, Genetics and Molecular Biology(all)
    • Immunology and Microbiology(all)

    Cite this

    Miura, Y., Matsui, S., Miyata, N., Harada, K., Kikkawa, Y., Ohmuraya, M., ... Tanaka, M. (2018). Differential expression of lutheran/BCAM regulates biliary tissue remodeling in ductular reaction during liver regeneration. eLife, 7, [e36572]. https://doi.org/10.7554/eLife.36572

    Differential expression of lutheran/BCAM regulates biliary tissue remodeling in ductular reaction during liver regeneration. / Miura, Yasushi; Matsui, Satoshi; Miyata, Naoko; Harada, Kenichi; Kikkawa, Yamato; Ohmuraya, Masaki; Araki, Kimi; Tsurusaki, Shinya; Okochi, Hitoshi; Goda, Nobuhito; Miyajima, Atsushi; Tanaka, Minoru.

    In: eLife, Vol. 7, e36572, 30.07.2018.

    Research output: Contribution to journalArticle

    Miura, Y, Matsui, S, Miyata, N, Harada, K, Kikkawa, Y, Ohmuraya, M, Araki, K, Tsurusaki, S, Okochi, H, Goda, N, Miyajima, A & Tanaka, M 2018, 'Differential expression of lutheran/BCAM regulates biliary tissue remodeling in ductular reaction during liver regeneration', eLife, vol. 7, e36572. https://doi.org/10.7554/eLife.36572
    Miura, Yasushi ; Matsui, Satoshi ; Miyata, Naoko ; Harada, Kenichi ; Kikkawa, Yamato ; Ohmuraya, Masaki ; Araki, Kimi ; Tsurusaki, Shinya ; Okochi, Hitoshi ; Goda, Nobuhito ; Miyajima, Atsushi ; Tanaka, Minoru. / Differential expression of lutheran/BCAM regulates biliary tissue remodeling in ductular reaction during liver regeneration. In: eLife. 2018 ; Vol. 7.
    @article{305ae9d9cb7d4d69ab16fede5863f26b,
    title = "Differential expression of lutheran/BCAM regulates biliary tissue remodeling in ductular reaction during liver regeneration",
    abstract = "Under chronic or severe liver injury, liver progenitor cells (LPCs) of biliary origin are known to expand and contribute to the regeneration of hepatocytes and cholangiocytes. This regeneration process is called ductular reaction (DR), which is accompanied by dynamic remodeling of biliary tissue. Although the DR shows apparently distinct mode of biliary extension depending on the type of liver injury, the key regulatory mechanism remains poorly understood. Here, we show that Lutheran (Lu)/Basal cell adhesion molecule (BCAM) regulates the morphogenesis of DR depending on liver disease models. Lu+ and Lu- 55 biliary cells isolated from injured liver exhibit opposite phenotypes in cell motility and duct formation capacities in vitro. By overexpression of Lu, Lu- biliary cells acquire the phenotype of Lu+ 57 biliary cells. Lu-deficient mice showed severe defects in DR. Our findings reveal a critical role of Lu in the control of phenotypic heterogeneity of DR in distinct liver disease models.",
    keywords = "Ductular reaction, Integrin β1, Laminin, Oval cell, Regeneration",
    author = "Yasushi Miura and Satoshi Matsui and Naoko Miyata and Kenichi Harada and Yamato Kikkawa and Masaki Ohmuraya and Kimi Araki and Shinya Tsurusaki and Hitoshi Okochi and Nobuhito Goda and Atsushi Miyajima and Minoru Tanaka",
    year = "2018",
    month = "7",
    day = "30",
    doi = "10.7554/eLife.36572",
    language = "English",
    volume = "7",
    journal = "eLife",
    issn = "2050-084X",
    publisher = "eLife Sciences Publications",

    }

    TY - JOUR

    T1 - Differential expression of lutheran/BCAM regulates biliary tissue remodeling in ductular reaction during liver regeneration

    AU - Miura, Yasushi

    AU - Matsui, Satoshi

    AU - Miyata, Naoko

    AU - Harada, Kenichi

    AU - Kikkawa, Yamato

    AU - Ohmuraya, Masaki

    AU - Araki, Kimi

    AU - Tsurusaki, Shinya

    AU - Okochi, Hitoshi

    AU - Goda, Nobuhito

    AU - Miyajima, Atsushi

    AU - Tanaka, Minoru

    PY - 2018/7/30

    Y1 - 2018/7/30

    N2 - Under chronic or severe liver injury, liver progenitor cells (LPCs) of biliary origin are known to expand and contribute to the regeneration of hepatocytes and cholangiocytes. This regeneration process is called ductular reaction (DR), which is accompanied by dynamic remodeling of biliary tissue. Although the DR shows apparently distinct mode of biliary extension depending on the type of liver injury, the key regulatory mechanism remains poorly understood. Here, we show that Lutheran (Lu)/Basal cell adhesion molecule (BCAM) regulates the morphogenesis of DR depending on liver disease models. Lu+ and Lu- 55 biliary cells isolated from injured liver exhibit opposite phenotypes in cell motility and duct formation capacities in vitro. By overexpression of Lu, Lu- biliary cells acquire the phenotype of Lu+ 57 biliary cells. Lu-deficient mice showed severe defects in DR. Our findings reveal a critical role of Lu in the control of phenotypic heterogeneity of DR in distinct liver disease models.

    AB - Under chronic or severe liver injury, liver progenitor cells (LPCs) of biliary origin are known to expand and contribute to the regeneration of hepatocytes and cholangiocytes. This regeneration process is called ductular reaction (DR), which is accompanied by dynamic remodeling of biliary tissue. Although the DR shows apparently distinct mode of biliary extension depending on the type of liver injury, the key regulatory mechanism remains poorly understood. Here, we show that Lutheran (Lu)/Basal cell adhesion molecule (BCAM) regulates the morphogenesis of DR depending on liver disease models. Lu+ and Lu- 55 biliary cells isolated from injured liver exhibit opposite phenotypes in cell motility and duct formation capacities in vitro. By overexpression of Lu, Lu- biliary cells acquire the phenotype of Lu+ 57 biliary cells. Lu-deficient mice showed severe defects in DR. Our findings reveal a critical role of Lu in the control of phenotypic heterogeneity of DR in distinct liver disease models.

    KW - Ductular reaction

    KW - Integrin β1

    KW - Laminin

    KW - Oval cell

    KW - Regeneration

    UR - http://www.scopus.com/inward/record.url?scp=85052074445&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=85052074445&partnerID=8YFLogxK

    U2 - 10.7554/eLife.36572

    DO - 10.7554/eLife.36572

    M3 - Article

    VL - 7

    JO - eLife

    JF - eLife

    SN - 2050-084X

    M1 - e36572

    ER -