Strategie antifibrotiche in modelli in vitro e in vivo di malattia infiammatoria intestinale

This study investigates intestinal fibrosis in inflammatory bowel disease (IBD), particularly Crohn’s Disease (CD), where fibrosis leads to complications like stenosis and fistulae. While current treatments focus on inflammation, effective anti-fibrotic therapies remain limited. The study evaluates commonly used IBD drugs for their ability to counteract fibrosis-related processes, specifically fibroblast activation and epithelial-to-mesenchymal transition (EMT). Among the tested drugs, prednisone, methylprednisolone, budesonide, and adalimumab effectively reduced fibrosis markers, with methylprednisolone, budesonide, and adalimumab also mitigating EMT. Additionally, the study examines losartan, an angiotensin II receptor blocker, for its anti-fibrotic potential. In vitro, losartan reversed angiotensin II-induced fibroblast activation and downregulated profibrotic genes. In vivo, using the SAMP mouse model of CD-like ileitis, losartan reduced inflammation and fibrosis, prevented fibrosis recurrence after steroid treatment, and downregulated AGTR1 expression. These findings suggest that losartan has direct anti-fibrotic effects independent of its anti-inflammatory properties, offering a potential new strategy for managing fibrosis in IBD.