2. Academic Validation
  3. Genetic disruption of the circadian gene Bmal1 in the intestinal epithelium reduces colonic inflammation

Genetic disruption of the circadian gene Bmal1 in the intestinal epithelium reduces colonic inflammation

  • EMBO Rep. 2025 Jun;26(12):3138-3161. doi: 10.1038/s44319-025-00464-y.
Shan Hua 1,  Ze Zhang 1,  Zhe Zhang 1,  Liansheng Liu 1,  Shicheng Yu 1,  Yanhui Xiao 1,  Yuan Liu 2,  Siting Wei 2,  Ying Xu 3,  Ye-Guang Chen 4 5 6
Affiliations

Affiliations

  • 1 Guangzhou National Laboratory, Guangzhou, 510005, China.
  • 2 The State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China.
  • 3 Cambridge-Su Genomic Resource Center, Soochow University, Suzhou, Jiangsu, 215123, China.
  • 4 Guangzhou National Laboratory, Guangzhou, 510005, China. ygchen@tsinghua.edu.cn.
  • 5 The State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China. ygchen@tsinghua.edu.cn.
  • 6 The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, School of Basic Medical Sciences, Institute of Biomedical Innovation, Jiangxi Medical College, Nanchang University, Nanchang, 330031, China. ygchen@tsinghua.edu.cn.
PMID: 40307620 DOI: 10.1038/s44319-025-00464-y
Abstract

Disruption of the circadian clock is associated with the development of inflammatory bowel disease (IBD), but the underlying mechanisms remain unclear. Here, we observe that mice in the early active phase (Zeitgeber time 12, ZT12) of the circadian clock are more tolerant to dextran sodium sulfate (DSS)-induced colitis, compared to those in the early resting phase (ZT0). The expression of the circadian gene Bmal1 peaks in the early resting phase and declines in the early active phase. Bmal1 knockout in the intestinal epithelium reduces DSS-induced inflammatory symptoms. Mechanistically, BMAL1 promotes Apoptosis by binding to apoptosis-related genes, including Bax, p53, and Bak1, and promotes their expression. Intriguingly, we observe circadian apoptotic rhythms in the homeostatic intestinal epithelium, while Bmal1 deletion reduces cell Apoptosis. Consistently, reducing Bmal1 expression by the REV-ERBα agonist SR9009 has the best therapeutic efficacy against DSS-induced colitis at ZT0. Collectively, our data demonstrate that the Bmal1-centered circadian clock is involved in intestinal injury repair.

Keywords

Bmal1; Circadian Rhythm; Colitis; Intestinal Homeostasis.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-16989
    99.46%, REV-ERB激动剂
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