IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v5y2014i1d10.1038_ncomms5573.html
   My bibliography  Save this article

PPARα-UGT axis activation represses intestinal FXR-FGF15 feedback signalling and exacerbates experimental colitis

Author

Listed:
  • Xueyan Zhou

    (State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University
    School of Pharmacy, Xuzhou Medical College)

  • Lijuan Cao

    (State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University)

  • Changtao Jiang

    (Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Yang Xie

    (State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University)

  • Xuefang Cheng

    (State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University)

  • Kristopher W. Krausz

    (Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Yunpeng Qi

    (Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Lu Sun

    (Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Yatrik M. Shah

    (University of Michigan Medical School
    University of Michigan Medical School)

  • Frank J. Gonzalez

    (Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Guangji Wang

    (State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University)

  • Haiping Hao

    (State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University)

Abstract

Bile acids play a pivotal role in the pathological development of inflammatory bowel disease (IBD). However, the mechanism of bile acid dysregulation in IBD remains unanswered. Here we show that intestinal peroxisome proliferator-activated receptor α (PPARα)-UDP-glucuronosyltransferases (UGTs) signalling is an important determinant of bile acid homeostasis. Dextran sulphate sodium (DSS)-induced colitis leads to accumulation of bile acids in inflamed colon tissues via activation of the intestinal peroxisome PPARα-UGTs pathway. UGTs accelerate the metabolic elimination of bile acids, and thereby decrease their intracellular levels in the small intestine. Reduced intracellular bile acids results in repressed farnesoid X receptor (FXR)-FGF15 signalling, leading to upregulation of hepatic CYP7A1, thus promoting the de novo bile acid synthesis. Both knockout of PPARα and treatment with recombinant FGF19 markedly attenuate DSS-induced colitis. Thus, we propose that intestinal PPARα-UGTs and downstream FXR-FGF15 signalling play vital roles in control of bile acid homeostasis and the pathological development of colitis.

Suggested Citation

  • Xueyan Zhou & Lijuan Cao & Changtao Jiang & Yang Xie & Xuefang Cheng & Kristopher W. Krausz & Yunpeng Qi & Lu Sun & Yatrik M. Shah & Frank J. Gonzalez & Guangji Wang & Haiping Hao, 2014. "PPARα-UGT axis activation represses intestinal FXR-FGF15 feedback signalling and exacerbates experimental colitis," Nature Communications, Nature, vol. 5(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5573
    DOI: 10.1038/ncomms5573
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms5573
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms5573?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
    ---><---

    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:5:y:2014:i:1:d:10.1038_ncomms5573. 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.