IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms13096.html
   My bibliography  Save this article

Macrophage-derived extracellular vesicle-packaged WNTs rescue intestinal stem cells and enhance survival after radiation injury

Author

Listed:
  • Subhrajit Saha

    (Albert Einstein College of Medicine & Montefiore Medical Center
    Present address: Department of Radiation Oncology University of Kansas Medical Center, Kansas City, Kansas 66160, USA
    Present address: Department of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas 66160, USA)

  • Evelyn Aranda

    (Albert Einstein College of Medicine)

  • Yoku Hayakawa

    (Irving Cancer Research Center, Columbia University)

  • Payel Bhanja

    (Albert Einstein College of Medicine & Montefiore Medical Center
    Present address: Department of Radiation Oncology University of Kansas Medical Center, Kansas City, Kansas 66160, USA)

  • Safinur Atay

    (University of Kansas Medical Center)

  • N Patrik Brodin

    (Albert Einstein College of Medicine & Montefiore Medical Center)

  • Jiufeng Li

    (Albert Einstein College of Medicine)

  • Samuel Asfaha

    (Irving Cancer Research Center, Columbia University)

  • Laibin Liu

    (Albert Einstein College of Medicine & Montefiore Medical Center)

  • Yagnesh Tailor

    (Irving Cancer Research Center, Columbia University)

  • Jinghang Zhang

    (Albert Einstein College of Medicine)

  • Andrew K. Godwin

    (University of Kansas Medical Center)

  • Wolfgang A. Tome

    (Albert Einstein College of Medicine & Montefiore Medical Center)

  • Timothy C. Wang

    (Irving Cancer Research Center, Columbia University)

  • Chandan Guha

    (Albert Einstein College of Medicine & Montefiore Medical Center
    Albert Einstein College of Medicine)

  • Jeffrey W. Pollard

    (Albert Einstein College of Medicine
    MRC Centre for Reproductive Health, University of Edinburgh)

Abstract

WNT/β-catenin signalling is crucial for intestinal homoeostasis. The intestinal epithelium and stroma are the major source of WNT ligands but their origin and role in intestinal stem cell (ISC) and epithelial repair remains unknown. Macrophages are a major constituent of the intestinal stroma. Here, we analyse the role of macrophage-derived WNT in intestinal repair in mice by inhibiting their release using a macrophage-restricted ablation of Porcupine, a gene essential for WNT synthesis. Such Porcn-depleted mice have normal intestinal morphology but are hypersensitive to radiation injury in the intestine compared with wild-type (WT) littermates. Porcn-null mice are rescued from radiation lethality by treatment with WT but not Porcn-null bone marrow macrophage-conditioned medium (CM). Depletion of extracellular vesicles (EV) from the macrophage CM removes WNT function and its ability to rescue ISCs from radiation lethality. Therefore macrophage-derived EV-packaged WNTs are essential for regenerative response of intestine against radiation.

Suggested Citation

  • Subhrajit Saha & Evelyn Aranda & Yoku Hayakawa & Payel Bhanja & Safinur Atay & N Patrik Brodin & Jiufeng Li & Samuel Asfaha & Laibin Liu & Yagnesh Tailor & Jinghang Zhang & Andrew K. Godwin & Wolfgang, 2016. "Macrophage-derived extracellular vesicle-packaged WNTs rescue intestinal stem cells and enhance survival after radiation injury," Nature Communications, Nature, vol. 7(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13096
    DOI: 10.1038/ncomms13096
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms13096
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms13096?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. Eun-Jung Kang & Jae-Hoon Kim & Young Eun Kim & Hana Lee & Kwang Bo Jung & Dong-Ho Chang & Youngjin Lee & Shinhye Park & Eun-Young Lee & Eun-Ji Lee & Ho Bum Kang & Moon-Young Rhyoo & Seungwoo Seo & Soh, 2024. "The secreted protein Amuc_1409 from Akkermansia muciniphila improves gut health through intestinal stem cell regulation," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    2. Camille Cohen & Rana Mhaidly & Hugo Croizer & Yann Kieffer & Renaud Leclere & Anne Vincent-Salomon & Catherine Robley & Dany Anglicheau & Marion Rabant & Aurélie Sannier & Marc-Olivier Timsit & Sean E, 2024. "WNT-dependent interaction between inflammatory fibroblasts and FOLR2+ macrophages promotes fibrosis in chronic kidney disease," Nature Communications, Nature, vol. 15(1), pages 1-23, 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:7:y:2016:i:1:d:10.1038_ncomms13096. 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.