This preprint is under consideration at Scientific Reports. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Michal Toborek
University of Miami Miller School of Medicine
Corresponding Author
License:
This work is licensed under a CC BY 4.0 License. Read Full License
We evaluated the mechanistic link between circadian rhythms and gut barrier permeability. Mice were subjected to either constant 24-hour light (LL) or 12-hour 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 an upstream regulator of Bmal1 and Clock. 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.
Keywords
circadian rhythm disruption, intestinal barrier integrity, ß-catenin, tight junction proteins, circadian clock genes, circadian rhythm molecules
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Loading...
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 19 Mar, 2021
No community comments so far
Reviewer #3 agreed
On 22 Mar, 2021
Review #5 received
Received 19 Mar, 2021
Review #6 received
Received 19 Mar, 2021
Review #1 received
Received 19 Mar, 2021
Review #7 received
Received 19 Mar, 2021
Review #4 received
Received 19 Mar, 2021
Review #3 received
Received 19 Mar, 2021
Reviewer #6 agreed
On 19 Mar, 2021
Reviewer #7 agreed
On 19 Mar, 2021
Reviewer #2 agreed
On 19 Mar, 2021
Reviewer #8 agreed
On 19 Mar, 2021
Reviewer #5 agreed
On 19 Mar, 2021
Reviewer #1 agreed
On 19 Mar, 2021
Reviewer #4 agreed
On 19 Mar, 2021
Reviewers invited
Invitations sent on 17 Mar, 2021
Editor assigned
On 17 Mar, 2021
Editor invited
On 17 Mar, 2021
Submission checks complete
On 17 Mar, 2021
First submitted
On 12 Mar, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
General Cell Biology & Physiology
Learn more about our company.
This preprint is under consideration at Scientific Reports. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Michal Toborek
University of Miami Miller School of Medicine
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 19 Mar, 2021
No community comments so far
Reviewer #3 agreed
On 22 Mar, 2021
Review #5 received
Received 19 Mar, 2021
Review #6 received
Received 19 Mar, 2021
Review #1 received
Received 19 Mar, 2021
Review #7 received
Received 19 Mar, 2021
Review #4 received
Received 19 Mar, 2021
Review #3 received
Received 19 Mar, 2021
Reviewer #6 agreed
On 19 Mar, 2021
Reviewer #7 agreed
On 19 Mar, 2021
Reviewer #2 agreed
On 19 Mar, 2021
Reviewer #8 agreed
On 19 Mar, 2021
Reviewer #5 agreed
On 19 Mar, 2021
Reviewer #1 agreed
On 19 Mar, 2021
Reviewer #4 agreed
On 19 Mar, 2021
Reviewers invited
Invitations sent on 17 Mar, 2021
Editor assigned
On 17 Mar, 2021
Editor invited
On 17 Mar, 2021
Submission checks complete
On 17 Mar, 2021
First submitted
On 12 Mar, 2021
Subject Areas
General Cell Biology & Physiology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
We evaluated the mechanistic link between circadian rhythms and gut barrier permeability. Mice were subjected to either constant 24-hour light (LL) or 12-hour 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 an upstream regulator of Bmal1 and Clock. 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.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Loading...