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.
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Posted 19 Mar, 2021
On 22 Mar, 2021
Received 19 Mar, 2021
Received 19 Mar, 2021
Received 19 Mar, 2021
Received 19 Mar, 2021
Received 19 Mar, 2021
Received 19 Mar, 2021
On 19 Mar, 2021
On 19 Mar, 2021
On 19 Mar, 2021
On 19 Mar, 2021
On 19 Mar, 2021
On 19 Mar, 2021
On 19 Mar, 2021
Invitations sent on 17 Mar, 2021
On 17 Mar, 2021
On 17 Mar, 2021
On 17 Mar, 2021
On 12 Mar, 2021
Posted 19 Mar, 2021
On 22 Mar, 2021
Received 19 Mar, 2021
Received 19 Mar, 2021
Received 19 Mar, 2021
Received 19 Mar, 2021
Received 19 Mar, 2021
Received 19 Mar, 2021
On 19 Mar, 2021
On 19 Mar, 2021
On 19 Mar, 2021
On 19 Mar, 2021
On 19 Mar, 2021
On 19 Mar, 2021
On 19 Mar, 2021
Invitations sent on 17 Mar, 2021
On 17 Mar, 2021
On 17 Mar, 2021
On 17 Mar, 2021
On 12 Mar, 2021
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
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