부산대학교 도서관

Crohn’s disease (CD) is a highly morbid chronic inflammatory disease. Many CD patients also develop fibrostenosing complications. However, there are no medical therapies for intestinal fibrosis. This is in part due to lack of high-fidelity biomimetic models to enhance understanding and drug development, which highlights a need to develop in vivomodels of inflammatory bowel disease-related intestinal fibrosis. This study investigates whether the TNFΔAREmouse, a model of ileal inflammation, also develops intestinal fibrosis. Several clinically relevant outcomes were studied including features of structural fibrosis, histological fibrosis, and gene expression. These include the use of a new luminal casting technique, traditional histological outcomes, use of second harmonic imaging, and quantitative PCR. These features were studied in aged TNFΔAREmice as well as in cohorts of numerous ages. At ages of 24+ weeks, TNFΔAREmice develop structural, histological, and transcriptional changes of ileal fibrosis. Protein and RNA expression profiles show changes as early as six weeks, coinciding with histological changes as early as 14-15 weeks, with overt structural fibrosis delayed until at least 16 weeks but most developed after 24 weeks. This study demonstrates that the TNFΔAREmouse is a viable and highly tractable model of ileal fibrosis. This model and the techniques employed can be leveraged for both mechanistic studies and therapeutic development for the treatment of intestinal fibrosis.