HISTOPATHOLOGICAL CHARACTERIZATION OF A CHRONIC DSS-INDUCED MOUSE MODEL OF IBD WITH INTESTINAL FIBROSIS

Abstract RATIONALE Inflammatory bowel disease (IBD) comprises a group of intestinal disorders, including ulcerative colitis and Crohn's disease. Intestinal fibrosis, as result chronic inflammation, is common complication in IBD. High treatment failure rates associated with existing interventions indicate high unmet need for more effective drugs to improve the management outcomes Consequently, translational animal models IBD demonstrating chronic, progressive colonic fibrosis are important tools preclinical drug discovery The aim present study was characterize histopathology DSS-induced mouse model METHODS Ten-weeks-old male C57BL/6JRj mice were randomized into groups based on body weight received 3 cycles DSS (2.5 % w/v) drinking water (DSS-IBD) or normal (CTRL). Terminal endpoints included colon morphometry quantitative histological markers inflammation assessed proximal, middle distal segments. Using RNA sequencing, transcriptome signatures profiled segment. RESULTS Compared healthy controls, DSS-IBD demonstrated hallmarks IBD, mild-to-moderate loss hypertrophy. Histopathological analysis indicated increased deposition inflammatory (CD45 CD11b), fibrogenesis (alpha-smooth muscle actin) (collagen 1a1, Picrosirius red) colon. Severe observed throughout all layers Histological findings supported by significantly upregulated gene expression fibrosis. CONCLUSIONS suitable testing novel therapies