Bibliographic Details
| Title: |
SIRT1 Stabilizes β-TrCP1 to Inhibit Snail1 Expression in Maintaining Intestinal Epithelial Integrity to Alleviate ColitisSummary |
| Authors: |
Liang Wang, Jinsong Li, Mingshan Jiang, Yue Luo, Xiaoke Xu, Juan Li, Yang Pan, Hu Zhang, Zhi-Xiong Jim Xiao, Yang Wang |
| Source: |
Cellular and Molecular Gastroenterology and Hepatology, Vol 18, Iss 2, Pp 101354- (2024) |
| Publisher Information: |
Elsevier, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Diseases of the digestive system. Gastroenterology |
| Subject Terms: |
SIRT1, β-TrCP1, Snail1, Inflammatory Bowel Disease, Intestinal Epithelial Integrity, Diseases of the digestive system. Gastroenterology, RC799-869 |
| More Details: |
Background & Aims: Dysfunction of the intestinal epithelial barrier comprising the junctional complex of tight junctions and adherent junctions leads to increased intestinal permeability, which is a major cause of uncontrolled inflammation related to inflammatory bowel disease (IBD). The NAD+-dependent deacetylase SIRT1 is implicated in inflammation and the pathologic process of IBD. We aimed to elucidate the protective role and underlying mechanism of SIRT1 in cell-cell junction and intestinal epithelial integrity. Methods: The correlation of SIRT1 expression and human IBD was analyzed by GEO or immunohistochemical analyses. BK5.mSIRT1 transgenic mice and wild-type mice were given dextran sodium sulfate (DSS) and the manifestation of colitis-related phenotypes was analyzed. Intestinal permeability was measured by FITC-dextran and cytokines expression was analyzed by quantitative polymerase chain reaction. The expression of the cell junction–related proteins in DSS-treated or SIRT1-knockdown Caco2 or HCT116 cells was analyzed by Western blotting. The effects of nicotinamide mononucleotide in DSS-induced mice colitis were investigated. Correlations of the SIRT1-β-TrCP1-Snail1-Occludin/Claudin-1/E-cadherin pathway with human IBD samples were analyzed. Results: Reduced SIRT1 expression is associated with human IBD specimens. SIRT1 transgenic mice exhibit much-reduced manifestations of DSS-induced colitis. The activation of SIRT1 by nicotinamide mononucleotide bolsters intestinal epithelial barrier function and ameliorates DSS-induced colitis in mice. Mechanistically, DSS downregulates SiRT1 expression, leading to destabilization of β-TrCP1 and upregulation of Snail1, accompanied by reduced expression of E-cadherin, Occludin, and Claudin-1, consequently resulting in increased epithelial permeability and inflammation. The deregulated SIRT1-β-TrCP1-Snail1-Occludin/Claudin-1/E-cadherin pathway correlates with human IBD. Conclusions: SIRT1 is pivotal in maintaining the intestinal epithelial barrier integrity via modulation of the β-TrCP1-Snail1-E-cadhein/Occludin/Claudin-1 pathway. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2352-345X |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S2352345X24001085; https://doaj.org/toc/2352-345X |
| DOI: |
10.1016/j.jcmgh.2024.05.002 |
| Access URL: |
https://doaj.org/article/c5a026f9ea6949e383cccb971f2274c9 |
| Accession Number: |
edsdoj.5a026f9ea6949e383cccb971f2274c9 |
| Database: |
Directory of Open Access Journals |
