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A gp130–Src–YAP module links inflammation to epithelial regeneration

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  • Koji Taniguchi

    (Laboratory of Gene Regulation and Signal Transduction, University of California, San Diego, La Jolla, California 92093, USA
    University of California, San Diego, La Jolla, California 92093, USA
    Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
    Keio University School of Medicine, Tokyo 160-8582, Japan)

  • Li-Wha Wu

    (Laboratory of Gene Regulation and Signal Transduction, University of California, San Diego, La Jolla, California 92093, USA
    Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan)

  • Sergei I. Grivennikov

    (Laboratory of Gene Regulation and Signal Transduction, University of California, San Diego, La Jolla, California 92093, USA
    Fox Chase Cancer Center, Cancer Prevention and Control Program)

  • Petrus R. de Jong

    (University of California, San Diego, La Jolla, California 92093, USA)

  • Ian Lian

    (University of California, San Diego, La Jolla, California 92093, USA
    Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, USA
    Lamar University, PO Box 10037, Beaumont, Texas 77710, USA)

  • Fa-Xing Yu

    (University of California, San Diego, La Jolla, California 92093, USA
    Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, USA
    Children’s Hospital and Institutes of Biomedical Sciences, Fudan University)

  • Kepeng Wang

    (Laboratory of Gene Regulation and Signal Transduction, University of California, San Diego, La Jolla, California 92093, USA)

  • Samuel B. Ho

    (VA San Diego Healthcare System)

  • Brigid S. Boland

    (Inflammatory Bowel Disease Center, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA)

  • John T. Chang

    (Inflammatory Bowel Disease Center, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA)

  • William J. Sandborn

    (Inflammatory Bowel Disease Center, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA)

  • Gary Hardiman

    (Medical University of South Carolina
    CSRC and BIMRC, San Diego State University)

  • Eyal Raz

    (University of California, San Diego, La Jolla, California 92093, USA)

  • Yoshihiko Maehara

    (Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan)

  • Akihiko Yoshimura

    (Keio University School of Medicine, Tokyo 160-8582, Japan
    Japan Science and Technology Agency, CREST, Tokyo 102-0076, Japan)

  • Jessica Zucman-Rossi

    (Inserm, UMR 1162, Génomique fonctionnelle des tumeurs solides, IUH, Paris 75010, France
    Université Paris Descartes, Labex Immuno-oncology, Sorbonne Paris Cité, Faculté de Medicine, Paris 75006, France)

  • Kun-Liang Guan

    (University of California, San Diego, La Jolla, California 92093, USA
    Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, USA)

  • Michael Karin

    (Laboratory of Gene Regulation and Signal Transduction, University of California, San Diego, La Jolla, California 92093, USA
    University of California, San Diego, La Jolla, California 92093, USA
    Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, USA)

Abstract

Inflammation promotes regeneration of injured tissues through poorly understood mechanisms, some of which involve interleukin (IL)-6 family members, the expression of which is elevated in many diseases including inflammatory bowel diseases and colorectal cancer. Here we show in mice and human cells that gp130, a co-receptor for IL-6 cytokines, triggers activation of YAP and Notch, transcriptional regulators that control tissue growth and regeneration, independently of the gp130 effector STAT3. Through YAP and Notch, intestinal gp130 signalling stimulates epithelial cell proliferation, causes aberrant differentiation and confers resistance to mucosal erosion. gp130 associates with the related tyrosine kinases Src and Yes, which are activated on receptor engagement to phosphorylate YAP and induce its stabilization and nuclear translocation. This signalling module is strongly activated upon mucosal injury to promote healing and maintain barrier function.

Suggested Citation

  • Koji Taniguchi & Li-Wha Wu & Sergei I. Grivennikov & Petrus R. de Jong & Ian Lian & Fa-Xing Yu & Kepeng Wang & Samuel B. Ho & Brigid S. Boland & John T. Chang & William J. Sandborn & Gary Hardiman & E, 2015. "A gp130–Src–YAP module links inflammation to epithelial regeneration," Nature, Nature, vol. 519(7541), pages 57-62, March.
    • Handle: RePEc:nat:nature:v:519:y:2015:i:7541:d:10.1038_nature14228
    DOI: 10.1038/nature14228
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