Inflammatory bowel disease (IBD), consisting of Crohn’s disease (CD) and ulcerative colitis (UC), involves chronic inflammation of all or part of the digestive tract and millions are affected around the world. Researchers currently believe that an unregulated immune response to resident intestinal bacteria, influenced by lifestyle and environmental factors, is responsible for the disruption of the complex immune balance in the bowel environment and the intestinal tissue damage.
However, the disease isn’t only restricted to the bowel and extraintestinal manifestations and complications are common in patients with inflammatory bowel disease (IBD) and can involve almost any organ or system. Indeed, inflammatory mediators can cause distant organ injury in many disease models. Previous studies have suggested the presence of an association between UC and kidney injury, but whether UC and kidney injury can be suppressed with anti-inflammatory therapy have never been examined.
The researchers examined the effect of dextran sulfate sodium (DSS)-induced colitis, with symptoms similar to human ulcerative colitis, on kidney injury and inflammation. In addition, they hypothesized that netrin-1, a guidance cue shown to have anti-apoptotic and anti-inflammatory functions in many models of acute and chronic diseases, could modulate colon-kidney cross talk through regulation of inflammation and apoptosis.
DSS induced colitis did indeed induced acute kidney injury in mice and overexpression of netrin-1 in epithelial cells reversed the effects and both suppressed colitis and colitis-induced acute kidney injury. Netrin-1’s protective effects were mediated through suppression of IL-6 as IL-6 knockout mice were resistant to colitis and acute kidney injury. Netrin-1 may reduce both IL-6 production and activity.
The researchers thus identified previously unrecognized cross talk between the colon and kidney. This is the first report that epithelial-specific overexpression of netrin-1 can suppress DSS induced colitis, inflammation, and acute kidney injury. Netrin-1 may limit distant organ injury by suppressing inflammatory mediators such as IL-6 and apoptosis. Overall, the study suggests that organ cross talk in DSS-induced colitis can be effectively treated with the anti-inflammatory molecule netrin-1.
Syncrosome is an Efficacy Characterization CRO that offers relevant disease models, cutting-edge techniques and a comprehensive background of physiopathology to assist drug discovery companies. Syncrosome uses DSS-rodent for drug screening and efficacy testing for Inflammatory Bowel disease (including Crohn’s disease et Ulcerative colitis).
Key words: preclinical CRO, preclinical study, animal model, disease model, animal research, DSS model, DSS – mouse model, Inflammatory Bowel disease, Crohn’s disease, Ulcerative colitis, gastrointestinal tract, inflammation, immune system, kidney, organ cross talk, efficacy testing, drug screening