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Circadian disruption alters gut barrier integrity via a ß-catenin-MMP-related pathway.
Mol. Cell. Biochem. 478, 581-595 (2023)
We evaluated the mechanistic link between circadian rhythms and gut barrier permeability. Mice were subjected to either constant 24-h light (LL) or 12-h light/dark cycles (LD). Mice housed in LL experienced a significant increase in gut barrier permeability that was associated with dysregulated ß-catenin expression and altered expression of tight junction (TJ) proteins. Silencing of ß-catenin resulted in disruption of barrier function in SW480 cells, with ß-catenin appearing to be an upstream regulator of the core circadian components, such as Bmal1, Clock, and Per1/2. In addition, ß-catenin silencing downregulated ZO-1 and occludin TJ proteins with only limited or no changes at their mRNA levels, suggesting post transcriptional regulation. Indeed, silencing of ß-catenin significantly upregulated expression of matrix metallopeptidase (MMP)-2 and MMP-9, and blocking MMP-2/9 activity attenuated epithelial disruption induced by ß-catenin silencing. These results indicate the regulatory role of circadian disruption on gut barrier integrity and the associations between TJ proteins and circadian rhythms, while demonstrating the regulatory role of ß-catenin in this process.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Circadian Clock Genes ; Circadian Rhythm Disruption ; Circadian Rhythm Molecules ; Intestinal Barrier Integrity ; ß-catenin ; Tight Junction Proteins
ISSN (print) / ISBN
0300-8177
e-ISSN
1573-4919
Quellenangaben
Volume: 478,
Issue: 3,
Pages: 581-595
Publisher
Springer
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Diabetes and Cancer (IDC)
Grants
NHLBI NIH HHS
NIDA NIH HHS
NIMH NIH HHS
NIDA NIH HHS
NIMH NIH HHS