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Transgenic overexpression of ITGB6 in intestinal epithelial cells exacerbates dextran sulfate sodium-induced colitis in mice.
- Source :
-
Journal of cellular and molecular medicine [J Cell Mol Med] 2021 Mar; Vol. 25 (5), pp. 2679-2690. Date of Electronic Publication: 2021 Jan 24. - Publication Year :
- 2021
-
Abstract
- Integrins, as a large family of cell adhesion molecules, play a crucial role in maintaining intestinal homeostasis. In inflammatory bowel disease (IBD), homeostasis is disrupted. Integrin αvβ6, which is mainly regulated by the integrin β6 subunit gene (ITGB6), is a cell adhesion molecule that mediates cell-cell and cell-matrix interactions. However, the role of ITGB6 in the pathogenesis of IBD remains elusive. In this study, we found that ITGB6 was markedly upregulated in inflamed intestinal tissues from patients with IBD. Then, we generated an intestinal epithelial cell-specific ITGB6 transgenic mouse model. Conditional ITGB6 transgene expression exacerbated experimental colitis in mouse models of acute and chronic dextran sulphate sodium (DSS)-induced colitis. Survival analyses revealed that ITGB6 transgene expression correlated with poor prognosis in DSS-induced colitis. Furthermore, our data indicated that ITGB6 transgene expression increased macrophages infiltration, pro-inflammatory cytokines secretion, integrin ligands expression and Stat1 signalling pathway activation. Collectively, our findings revealed a previously unknown role of ITGB6 in IBD and highlighted the possibility of ITGB6 as a diagnostic marker and therapeutic target for IBD.<br /> (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
- Subjects :
- Animals
Biomarkers
Colitis pathology
Cytokines metabolism
Dextran Sulfate adverse effects
Disease Models, Animal
Disease Susceptibility
Epithelial Cells pathology
Gene Expression Profiling
Gene Targeting
Genetic Vectors genetics
Humans
Inflammation Mediators metabolism
Integrin beta Chains metabolism
Intestinal Mucosa pathology
Macrophages immunology
Macrophages metabolism
Macrophages pathology
Mice
Mice, Transgenic
Colitis etiology
Colitis metabolism
Epithelial Cells metabolism
Gene Expression
Integrin beta Chains genetics
Intestinal Mucosa metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1582-4934
- Volume :
- 25
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of cellular and molecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 33491282
- Full Text :
- https://doi.org/10.1111/jcmm.16297