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P074. Extracellular matrix protein expression in chronic repeated DSS colitis reflects transmural remodeling in human Crohn's disease

C. Breynaert1, J. Cremer1, C. Perrier1, M. Ferrante1, S. Vermeire1, P. Rutgeerts1, J. Ceuppens2, K. Geboes3, G. Van Assche1, 1KU Leuven, TARGID, Leuven, Belgium, 2KU Leuven, Clinical immunology, Leuven, Belgium, 3KU Leuven, Translational Cell and Tissue Research, Leuven, Belgium

Background

Crohn's disease (CD) is characterized by transmural inflammation and connective tissue remodelling as evidenced by profound changes in extracellular matrix (ECM) deposition. Correlates in animal models are lacking. We aimed to investigate ECM protein expression in a model of murine chronic relapsing colitis characterized by segmental, transmural inflammation with lymphoid aggregates and collagen deposition.

Methods

Acute and chronic relapsing colonic inflammation was induced in C57/BL6 mice using several cycles of exposure to DSS in drinking water followed by recovery phases. α-smooth muscle actin (α-SMA), vimentin, tenascin C and collagen I and III were studied using immunohistochemistry.

Results

Chronic DSS colitis induced persistent thickening of the muscularis propria (MP) with infiltration of vimentin+ cells in the chronic phase but not in acute colitis. Moreover, a mucosal healing response was associated with more cycles and recovery. Myofibroblasts (vimentin+ α-SMA+) were present in the submucosa (SM) in the chronic phase and not in the acute model. Differential deposition of collagen I and III was observed: collagen I was present in the SM around vimentin+ cells. Collagen III deposition in the SM started in the acute phase, further increased in chronic colitis with infiltration of collagen III between smooth muscle cells of the MP, to intestinal stricture formation in CD. During prolonged recovery there was a decrease in collagen III. Tenascin expression was scant in control colon but was clearly present in the mucosa and SM in the acute phase in individual cells. A linear deposition of tenascin around the crypts was also seen as expected in acute colitis. The linear deposition in the mucosa and submucosal spots persisted after 2 cycles of DSS, correlating with persisting tissue damage. The expression of tenascin decreased after 3 cycles and more so after additional recovery, in association with the disappearance of tissue damage.

Figure: Set-up of the study.

Conclusion

The connective tissue changes observed in chronic murine colitis induced by repeated cycles of DSS reflects tissue remodeling as seen in CD. The technical ease and reproducibility of the DSS model and ability to induce it in mice of a common inbred strain makes it an attractive model to study the connective tissue changes occurring in IBD.