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Status |
Public on Sep 30, 2019 |
Title |
RORa Controls Intestinal Homeostasis via Negative Regulation of NF-kB Signaling Pathway |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
A member of the nuclear receptors, retinoic acid-related orphan receptor a (RORa) is an important transcription factor for various biological processes including circadian rhythm, metabolic regulation, immune cell development and cancer. Here we found that RORa is important for intestinal homeostasis by negatively regulating the transcriptional activity of NF-kB, a major inflammatory regulator in intestinal epithelial cells. Intestinal Rora-deficient mice found were highly susceptible to DSS-induced injury. Transcriptome analysis showed that intestine-specific Rora deletion causes regulatory impairment of NF-kB signaling leading to excessive inflammatory responses. RORa specifically binds to the NF-kB target promoter and inhibits transcriptional activity for transcriptional repression of NF-kB activity via histone deacetylase 3 (HDAC3). Taken together, RORa plays a pivotal role in the homeostatic regulation of intestinal epithelial cells in inflammatory conditions. Therefore, therapeutic strategies designed to modulate RORa activity may be beneficial in the treatment of chronic inflammatory diseases such as Inflammatory bowel disease (IBD).
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Overall design |
Gene expression profiling of RORaf/f and intestine-specific Rora knock-out (RORaΔIEC) Intestinal Ephithelial Cell (IEC) untreated or treated with DSS.
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Contributor(s) |
Kim D, Park D, Baek S |
Citation missing |
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Submission date |
Oct 30, 2018 |
Last update date |
Oct 02, 2019 |
Contact name |
Dongha Kim |
E-mail(s) |
hidongha@gmail.com
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Organization name |
Seoul National University
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Street address |
599 Gwanak-ro
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City |
Seoul |
ZIP/Postal code |
08826 |
Country |
South Korea |
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Platforms (1) |
GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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Samples (8)
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Relations |
BioProject |
PRJNA501886 |
SRA |
SRP167246 |