| First Author | Kopecki Z | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 12792 |
| PubMed ID | 31488864 | Mgi Jnum | J:285304 |
| Mgi Id | MGI:6389519 | Doi | 10.1038/s41598-019-49129-6 |
| Citation | Kopecki Z, et al. (2019) Flightless I exacerbation of inflammatory responses contributes to increased colonic damage in a mouse model of dextran sulphate sodium-induced ulcerative colitis. Sci Rep 9(1):12792 |
| abstractText | Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by cytokine driven inflammation that disrupts the mucosa and impedes intestinal structure and functions. Flightless I (Flii) is an immuno-modulatory protein is a member of the gelsolin family of actin-remodelling proteins that regulates cellular and inflammatory processes critical in tissue repair. Here we investigated its involvement in UC and show that Flii is significantly elevated in colonic tissues of patients with inflammatory bowel disease. Using an acute murine model of colitis, we characterised the contribution of Flii to UC using mice with low (Flii(+/-)), normal (Flii(+/+)) and high Flii (Flii(Tg/Tg)). High levels of Flii resulted in significantly elevated disease severity index scores, increased rectal bleeding and degree of colon shortening whereas, low Flii expression decreased disease severity, reduced tissue inflammation and improved clinical indicators of UC. Mice with high levels of Flii had significantly increased histological disease severity and elevated mucosal damage with significantly increased inflammatory cell infiltrate and significantly higher levels of TNF-alpha, IFN-gamma, IL-5 and IL-13 pro-inflammatory cytokines. Additionally, Flii overexpression resulted in decreased beta-catenin levels, inhibited Wnt/beta-catenin signalling and impaired regeneration of colonic crypts. These studies suggest that high levels of Flii, as is observed in patients with UC, may adversely affect mucosal healing via mechanisms involving Th1 and Th2 mediated tissue inflammation and Wnt/beta-catenin signalling pathway. |
