0 193

Cited 3 times in

RORα is crucial for attenuated inflammatory response to maintain intestinal homeostasis

Authors
 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 
Citation
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol.116(42) : 21140-21149, 2019 
Journal Title
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 
ISSN
 0027-8424 
Issue Date
2019
Keywords
HDAC3 ; NF-kB signaling ; RORα ; epigenetic regulation ; inflammation
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).
Full Text
https://www.pnas.org/content/116/42/21140.long
DOI
10.1073/pnas.1907595116
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Im, Sun-Kyoung(임선경)
Fang, Sungsoon(황성순) ORCID logo https://orcid.org/0000-0003-0201-5567
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/173069
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links