REV-ERBα integrates colon clock with experimental colitis through regulation of NF-κB/NLRP3 axis

Shuai Wang, Yanke Lin, Xue Yuan, Feng Li, Lianxia Guo and Baojian Wu ()
Additional contact information
Shuai Wang: Jinan University
Yanke Lin: Jinan University
Xue Yuan: Jinan University
Feng Li: Jinan University
Lianxia Guo: Jinan University
Baojian Wu: Jinan University

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract The roles of Rev-erbα and circadian clock in colonic inflammation remain unclarified. Here we show colon clock genes (including Rev-erbα) are dysregulated in mice with DSS-induced colitis. In turn, disruption of the circadian clock exacerbates experimental colitis. Rev-erbα-deficient mice are more sensitive to DSS-induced colitis, supporting a critical role of Rev-erbα in disease development. Further, Rev-erbα ablation causes activation of Nlrp3 inflammasome in mice. Cell-based experiments reveal Rev-erbα inactivates Nlrp3 inflammasome mainly at the priming stage. Rev-erbα directly represses Nlrp3 transcription through specific binding to the promoter region. Additionally, Rev-erbα represses p65 transcription and indirectly repressed Nlrp3 via the NF-κB pathway. Interestingly, Rev-erbα activation in wild-type mice by SR9009 attenuates DSS-induced colitis, whereas the protective effects are lost in Nlrp3−/− and Rev-erbα−/− mice. Taken together, Rev-erbα regulates experimental colitis through its repressive action on the NF-κB/Nlrp3 axis. Targeting Rev-erbα may represent a promising approach for prevention and management of colitis.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-018-06568-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06568-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-06568-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().