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Eum, S.Y.* ; Schurhoff, N.* ; Teglas, T.* ; Wolff, G. ; Toborek, M.*

Circadian disruption alters gut barrier integrity via a ß-catenin-MMP-related pathway.

Mol. Cell. Biochem. 478, 581-595 (2023)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter 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 Band: 478, Heft: 3, Seiten: 581-595 Artikelnummer: , Supplement: ,
Verlag Springer
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Förderungen NHLBI NIH HHS
NIDA NIH HHS
NIMH NIH HHS