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

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    2 Citations (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

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    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., 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, 7, [e36572]. https://doi.org/10.7554/eLife.36572