A new player in Stricturing Crohn’s Disease: implication for pathogenesis and new therapeutic strategies

Intestinal fibrosis is a common complication of several enteropathies with inflammatory bowel disease (IBD) being the major cause. Despite remarkable therapeutic progress in the management of inflammation, limited progress has occurred with respect to a specific anti-fibrotic therapy for IBD. Surgery is still the only practical solution for patients with complications secondary to intestinal fibrosis, and postsurgical recurrence is frequent. It is now evident that control of intestinal inflammation does not necessarily affect the associated fibrotic process. For this reason, specific anti-fibrotic strategies are urgently required for the treatment of this disease. In recent years it has become apparent that integrins have profound effects on tissue fibrosis in multiple organs. In fact, many of the key cell-cell and cell-matrix interactions that regulate fibrosis are mediated by members of the integrin family. Alpha 7 integrin belongs to this family, and is a key element in muscle cells’ biological functions; however, its characterization in the gut and its role in fibrogenesis has never been explored. Findings from this project revealed for the first time a contribution for this integrin in the development of intestinal fibrosis. Using both in vitro and in vivo approaches we define α7 integrin as a potential therapeutic target for IBD patients with fibrotic complications; moreover, with the use of an original therapeutic strategy, that foreseen the use of calcium phosphate nanoparticles to deliver siRNA against the α7 integrin gene (ITGA7) in the gut, we promote the generated ITGA7 RNAi as a candidate drug for the treatment of fibrostenotic IBD patients. Results from this project may radically change the way to diagnose, prevent and treat intestinal fibrosis.