Skip to main content
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian
  • Log in
  • My Cart

Main menu

  • Home
  • Articles
    • Current
    • Latest Articles
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • Archive
  • Front Matter
  • News
    • For the Press
    • Highlights from Latest Articles
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Purpose and Scope
    • Editorial and Journal Policies
    • Submission Procedures
    • For Reviewers
    • Author FAQ
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian

User menu

  • Log in
  • My Cart

Search

  • Advanced search
Home
Home

Advanced Search

  • Home
  • Articles
    • Current
    • Latest Articles
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • Archive
  • Front Matter
  • News
    • For the Press
    • Highlights from Latest Articles
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Purpose and Scope
    • Editorial and Journal Policies
    • Submission Procedures
    • For Reviewers
    • Author FAQ

New Research In

Physical Sciences

Featured Portals

  • Physics
  • Chemistry
  • Sustainability Science

Articles by Topic

  • Applied Mathematics
  • Applied Physical Sciences
  • Astronomy
  • Computer Sciences
  • Earth, Atmospheric, and Planetary Sciences
  • Engineering
  • Environmental Sciences
  • Mathematics
  • Statistics

Social Sciences

Featured Portals

  • Anthropology
  • Sustainability Science

Articles by Topic

  • Economic Sciences
  • Environmental Sciences
  • Political Sciences
  • Psychological and Cognitive Sciences
  • Social Sciences

Biological Sciences

Featured Portals

  • Sustainability Science

Articles by Topic

  • Agricultural Sciences
  • Anthropology
  • Applied Biological Sciences
  • Biochemistry
  • Biophysics and Computational Biology
  • Cell Biology
  • Developmental Biology
  • Ecology
  • Environmental Sciences
  • Evolution
  • Genetics
  • Immunology and Inflammation
  • Medical Sciences
  • Microbiology
  • Neuroscience
  • Pharmacology
  • Physiology
  • Plant Biology
  • Population Biology
  • Psychological and Cognitive Sciences
  • Sustainability Science
  • Systems Biology
Research Article

RORα is crucial for attenuated inflammatory response to maintain intestinal homeostasis

Se Kyu Oh, Dongha Kim, Kyeongkyu Kim, Kyungjin Boo, Young Suk Yu, Ik Soo Kim, Yoon Jeon, Sun-Kyoung Im, Su-Hyung Lee, Ji Min Lee, Younhee Ko, Ho Lee, Daechan Park, Sungsoon Fang, and Sung Hee Baek
PNAS October 15, 2019 116 (42) 21140-21149; first published September 30, 2019 https://doi.org/10.1073/pnas.1907595116
Se Kyu Oh
aCreative Research Initiatives Center for Epigenetic Code and Diseases, School of Biological Sciences, Seoul National University, 08826 Seoul, South Korea;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dongha Kim
aCreative Research Initiatives Center for Epigenetic Code and Diseases, School of Biological Sciences, Seoul National University, 08826 Seoul, South Korea;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kyeongkyu Kim
aCreative Research Initiatives Center for Epigenetic Code and Diseases, School of Biological Sciences, Seoul National University, 08826 Seoul, South Korea;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kyungjin Boo
aCreative Research Initiatives Center for Epigenetic Code and Diseases, School of Biological Sciences, Seoul National University, 08826 Seoul, South Korea;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Young Suk Yu
aCreative Research Initiatives Center for Epigenetic Code and Diseases, School of Biological Sciences, Seoul National University, 08826 Seoul, South Korea;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ik Soo Kim
aCreative Research Initiatives Center for Epigenetic Code and Diseases, School of Biological Sciences, Seoul National University, 08826 Seoul, South Korea;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yoon Jeon
bGraduate School of Cancer Science and Policy, Research Institute, National Cancer Center, 10408 Goyang, South Korea;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sun-Kyoung Im
cSeverance Biomedical Science Institute, BK21 Plus Project for Medical Science, Gangnam Severance Hospital, Yonsei University College of Medicine, 06273 Seoul, South Korea;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Su-Hyung Lee
dBranch of Carcinogenesis and Metastasis, Research Institute, National Cancer Center, 10408 Goyang, South Korea;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ji Min Lee
eDepartment of Molecular Bioscience, College of Biomedical Sciences, Kangwon National University, 24341 Chuncheon, South Korea;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Younhee Ko
fDivision of Biomedical Engineering, Hankuk University of Foreign Studies, 17035 Yongin, South Korea;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ho Lee
bGraduate School of Cancer Science and Policy, Research Institute, National Cancer Center, 10408 Goyang, South Korea;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Daechan Park
gDepartment of Biological Sciences, College of Natural Sciences, Ajou University, 16499 Suwon, South Korea
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: dpark@ajou.ac.kr sfang@yuhs.ac.kr sbaek@snu.ac.kr
Sungsoon Fang
cSeverance Biomedical Science Institute, BK21 Plus Project for Medical Science, Gangnam Severance Hospital, Yonsei University College of Medicine, 06273 Seoul, South Korea;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: dpark@ajou.ac.kr sfang@yuhs.ac.kr sbaek@snu.ac.kr
Sung Hee Baek
aCreative Research Initiatives Center for Epigenetic Code and Diseases, School of Biological Sciences, Seoul National University, 08826 Seoul, South Korea;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: dpark@ajou.ac.kr sfang@yuhs.ac.kr sbaek@snu.ac.kr
  1. Edited by David D. Moore, Baylor College of Medicine, Houston, TX, and approved September 12, 2019 (received for review May 3, 2019)

  • Article
  • Figures & SI
  • Info & Metrics
  • PDF
Loading

This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.

Significance

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, and the worldwide prevalence of IBD rapidly continues to rise. It has been widely accepted that genetic predisposition remains an important risk factor of IBD in addition to microbiota, dietary environment, and immune response. In this study, we demonstrated that retinoic acid-related orphan receptor α (RORα) controls the inflammatory signaling network to maintain homeostasis in vivo in intestinal epithelium. Our study strongly proposes that RORα is a therapeutic target for the treatment of IBD.

Abstract

Retinoic acid-related orphan receptor α (RORα) functions as a transcription factor for various biological processes, including circadian rhythm, cancer, and metabolism. Here, we generate intestinal epithelial cell (IEC)-specific RORα-deficient (RORαΔIEC) mice and find that RORα is crucial for maintaining intestinal homeostasis by attenuating nuclear factor κB (NF-κB) transcriptional activity. RORαΔIEC mice exhibit excessive intestinal inflammation and highly activated inflammatory responses in the dextran sulfate sodium (DSS) mouse colitis model. Transcriptome analysis reveals that deletion of RORα leads to up-regulation of NF-κB target genes in IECs. Chromatin immunoprecipitation analysis reveals corecruitment of RORα and histone deacetylase 3 (HDAC3) on NF-κB target promoters and subsequent dismissal of CREB binding protein (CBP) and bromodomain-containing protein 4 (BRD4) for transcriptional repression. Together, we demonstrate that RORα/HDAC3-mediated attenuation of NF-κB signaling controls the balance of inflammatory responses, and therapeutic strategies targeting this epigenetic regulation could be beneficial to the treatment of chronic inflammatory diseases, including inflammatory bowel disease (IBD).

  • epigenetic regulation
  • inflammation
  • RORα
  • HDAC3
  • NF-kB signaling

Footnotes

  • ↵1S.K.O. and D.K. contributed equally to this work.

  • ↵2To whom correspondence may be addressed. Email: dpark{at}ajou.ac.kr, sfang{at}yuhs.ac.kr, or sbaek{at}snu.ac.kr.
  • Author contributions: S.K.O., D.K., K.K., I.S.K., J.M.L., and S.H.B. designed research; S.K.O., D.K., K.K., S.-K.I., and S.F. performed research; S.K.O., K.K., K.B., Y.J., and H.L. contributed new reagents/analytic tools; S.K.O., D.K., K.K., Y.S.Y., S.-H.L., Y.K., D.P., and S.F. analyzed data; and S.K.O., D.K., D.P., S.F., and S.H.B. wrote the paper.

  • The authors declare no competing interest.

  • This article is a PNAS Direct Submission.

  • Data deposition: The data reported in this paper have been deposited in the Gene Expression Omnibus (GEO) database, https://www.ncbi.nlm.nih.gov/geo (accession no. GSE121977).

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1907595116/-/DCSupplemental.

Published under the PNAS license.

View Full Text

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.

Subscribers, for more details, please visit our Subscriptions FAQ.

Please click here to log into the PNAS submission website.

PreviousNext
Back to top
Article Alerts
Email Article

Thank you for your interest in spreading the word on PNAS.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
RORα is crucial for attenuated inflammatory response to maintain intestinal homeostasis
(Your Name) has sent you a message from PNAS
(Your Name) thought you would like to see the PNAS web site.
Citation Tools
RORα is crucial for attenuated inflammatory response to maintain intestinal homeostasis
Se Kyu Oh, Dongha Kim, Kyeongkyu Kim, Kyungjin Boo, Young Suk Yu, Ik Soo Kim, Yoon Jeon, Sun-Kyoung Im, Su-Hyung Lee, Ji Min Lee, Younhee Ko, Ho Lee, Daechan Park, Sungsoon Fang, Sung Hee Baek
Proceedings of the National Academy of Sciences Oct 2019, 116 (42) 21140-21149; DOI: 10.1073/pnas.1907595116

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
RORα is crucial for attenuated inflammatory response to maintain intestinal homeostasis
Se Kyu Oh, Dongha Kim, Kyeongkyu Kim, Kyungjin Boo, Young Suk Yu, Ik Soo Kim, Yoon Jeon, Sun-Kyoung Im, Su-Hyung Lee, Ji Min Lee, Younhee Ko, Ho Lee, Daechan Park, Sungsoon Fang, Sung Hee Baek
Proceedings of the National Academy of Sciences Oct 2019, 116 (42) 21140-21149; DOI: 10.1073/pnas.1907595116
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Mendeley logo Mendeley
Proceedings of the National Academy of Sciences: 116 (50)
Current Issue

Submit

Sign up for Article Alerts

Article Classifications

  • Biological Sciences
  • Immunology and Inflammation

Jump to section

  • Article
    • Abstract
    • Results
    • Discussion
    • Materials and Methods
    • Acknowledgments
    • Footnotes
    • References
  • Figures & SI
  • Info & Metrics
  • PDF

You May Also be Interested in

Modulating the body's networks could become mainstream therapy for many health issues. Image credit: The Feinstein Institutes for Medicine Research.
Core Concept: The rise of bioelectric medicine sparks interest among researchers, patients, and industry
Modulating the body's networks could become mainstream therapy for many health issues.
Image credit: The Feinstein Institutes for Medicine Research.
Adaptations in heart structure and function likely enabled endurance and survival in preindustrial humans. Image courtesy of Pixabay/Skeeze.
Human heart evolved for endurance
Adaptations in heart structure and function likely enabled endurance and survival in preindustrial humans.
Image courtesy of Pixabay/Skeeze.
Viscoelastic carrier fluids enhance retention of fire retardants on wildfire-prone vegetation. Image courtesy of Jesse D. Acosta.
Viscoelastic fluids and wildfire prevention
Viscoelastic carrier fluids enhance retention of fire retardants on wildfire-prone vegetation.
Image courtesy of Jesse D. Acosta.
Water requirements may make desert bird declines more likely in a warming climate. Image courtesy of Sean Peterson (photographer).
Climate change and desert bird collapse
Water requirements may make desert bird declines more likely in a warming climate.
Image courtesy of Sean Peterson (photographer).
QnAs with NAS member and plant biologist Sheng Yang He. Image courtesy of Sheng Yang He.
Featured QnAs
QnAs with NAS member and plant biologist Sheng Yang He
Image courtesy of Sheng Yang He.

Similar Articles

Site Logo
Powered by HighWire
  • Submit Manuscript
  • Twitter
  • Facebook
  • RSS Feeds
  • Email Alerts

Articles

  • Current Issue
  • Latest Articles
  • Archive

PNAS Portals

  • Classics
  • Front Matter
  • Teaching Resources
  • Anthropology
  • Chemistry
  • Physics
  • Sustainability Science

Information

  • Authors
  • Editorial Board
  • Reviewers
  • Press
  • Site Map
  • PNAS Updates

Feedback    Privacy/Legal

Copyright © 2019 National Academy of Sciences. Online ISSN 1091-6490