IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-07747-0.html
   My bibliography  Save this article

Vagus-macrophage-hepatocyte link promotes post-injury liver regeneration and whole-body survival through hepatic FoxM1 activation

Author

Listed:
  • Tomohito Izumi

    (Tohoku University Graduate School of Medicine)

  • Junta Imai

    (Tohoku University Graduate School of Medicine
    PRIME)

  • Junpei Yamamoto

    (Tohoku University Graduate School of Medicine)

  • Yohei Kawana

    (Tohoku University Graduate School of Medicine)

  • Akira Endo

    (Tohoku University Graduate School of Medicine)

  • Hiroto Sugawara

    (Tohoku University Graduate School of Medicine)

  • Masato Kohata

    (Tohoku University Graduate School of Medicine)

  • Yoichiro Asai

    (Tohoku University Graduate School of Medicine)

  • Kei Takahashi

    (Tohoku University Graduate School of Medicine)

  • Shinjiro Kodama

    (Tohoku University Graduate School of Medicine)

  • Keizo Kaneko

    (Tohoku University Graduate School of Medicine)

  • Junhong Gao

    (Tohoku University Graduate School of Medicine)

  • Kenji Uno

    (Tohoku University Graduate School of Medicine)

  • Shojiro Sawada

    (Tohoku University Graduate School of Medicine)

  • Vladimir V. Kalinichenko

    (Division of Pulmonary Biology, Cincinnati Children’s Hospital Medical Center)

  • Yasushi Ishigaki

    (Tohoku University Graduate School of Medicine
    Iwate Medical University)

  • Tetsuya Yamada

    (Tohoku University Graduate School of Medicine)

  • Hideki Katagiri

    (Tohoku University Graduate School of Medicine
    Japan Agency for Medical Research and Development, CREST)

Abstract

The liver possesses a high regenerative capacity. Liver regeneration is a compensatory response overcoming disturbances of whole-body homeostasis provoked by organ defects. Here we show that a vagus-macrophage-hepatocyte link regulates acute liver regeneration after liver injury and that this system is critical for promoting survival. Hepatic Foxm1 is rapidly upregulated after partial hepatectomy (PHx). Hepatic branch vagotomy (HV) suppresses this upregulation and hepatocyte proliferation, thereby increasing mortality. In addition, hepatic FoxM1 supplementation in vagotomized mice reverses the suppression of liver regeneration and blocks the increase in post-PHx mortality. Hepatic macrophage depletion suppresses both post-PHx Foxm1 upregulation and remnant liver regeneration, and increases mortality. Hepatic Il-6 rises rapidly after PHx and this is suppressed by HV, muscarinic blockade or resident macrophage depletion. Furthermore, IL-6 neutralization suppresses post-PHx Foxm1 upregulation and remnant liver regeneration. Collectively, vagal signal-mediated IL-6 production in hepatic macrophages upregulates hepatocyte FoxM1, leading to liver regeneration and assures survival.

Suggested Citation

  • Tomohito Izumi & Junta Imai & Junpei Yamamoto & Yohei Kawana & Akira Endo & Hiroto Sugawara & Masato Kohata & Yoichiro Asai & Kei Takahashi & Shinjiro Kodama & Keizo Kaneko & Junhong Gao & Kenji Uno &, 2018. "Vagus-macrophage-hepatocyte link promotes post-injury liver regeneration and whole-body survival through hepatic FoxM1 activation," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07747-0
    DOI: 10.1038/s41467-018-07747-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-07747-0
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-018-07747-0?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Hiroto Sugawara & Junta Imai & Junpei Yamamoto & Tomohito Izumi & Yohei Kawana & Akira Endo & Masato Kohata & Junro Seike & Haremaru Kubo & Hiroshi Komamura & Yuichiro Munakata & Yoichiro Asai & Shini, 2023. "A highly sensitive strategy for monitoring real-time proliferation of targeted cell types in vivo," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07747-0. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.