Transgenic overexpression of ITGB6 in intestinal epithelial cells exacerbates dextran sulfate sodium‐induced colitis in mice
Open Access
- 24 January 2021
- journal article
- research article
- Published by Wiley in Journal of Cellular and Molecular Medicine
- Vol. 25 (5), 2679-2690
- https://doi.org/10.1111/jcmm.16297
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 alpha v beta 6, which is mainly regulated by the integrin beta 6 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.Keywords
Funding Information
- National Natural Science Foundation of China (81672342, 81772527, 81302072)
- Fundamental Research Funds for the Central Universities (2019QNA7028, 2019FZJD009)
This publication has 52 references indexed in Scilit:
- Resident and pro-inflammatory macrophages in the colon represent alternative context-dependent fates of the same Ly6Chi monocyte precursorsMucosal Immunology, 2013
- Ly6Chi Monocytes in the Inflamed Colon Give Rise to Proinflammatory Effector Cells and Migratory Antigen-Presenting CellsImmunity, 2012
- IL-1β mediates chronic intestinal inflammation by promoting the accumulation of IL-17A secreting innate lymphoid cells and CD4+ Th17 cellsThe Journal of Experimental Medicine, 2012
- Inflammation switches the differentiation program of Ly6Chi monocytes from antiinflammatory macrophages to inflammatory dendritic cells in the colonThe Journal of Experimental Medicine, 2012
- Intestinal homeostasis and its breakdown in inflammatory bowel diseaseNature, 2011
- CX3CR1 defines functionally distinct intestinal mononuclear phagocyte subsets which maintain their respective functions during homeostatic and inflammatory conditionsEuropean Journal of Immunology, 2011
- Natalizumab for the Treatment of Active Crohn’s Disease: Results of the ENCORE TrialGastroenterology, 2007
- Expression of interleukin 1β and interleukin 1β converting enzyme by intestinal macrophages in health and inflammatory bowel diseaseGut, 1998
- Lymphocyte Homing and HomeostasisScience, 1996
- SIMPLE INDEX OF CROHN'S DISEASE ACTIVITYThe Lancet, 1980