Inflammatory bowel disease and extracellular matrix: when victim becomes double agent

The extracellular matrix (ECM) represents an intricate network of proteins present in all organs, with specific physical and biochemical functions. ECM is composed of two distinct but connected entities: the basement membrane, located beneath the epithelium, and the interstitial matrix, present in the mucosa and submucosa. Physiologically, ECM modulates several functions, including epithelium turnover, intercellular communications, cell adhesion, differentiation, proliferation, apoptosis, and tissue remodeling.

After an injury, the epithelial barrier fails, affecting the ECM structure and functions. The normal gut structure and functions depend on ECM, which is regulated by ECM-producing cells/ECM-degrading enzymes. Intestinal injury can lead to epithelial barrier disruption and then to acute mucosal inflammation that can heal or become chronic. The ECM is directly involved in mucosal healing, while the key mechanisms leading to the chronicity of intestinal inflammation are unknown. Inflammatory cells release countless cytokines, chemokines, and growth factors, which, by interacting with specific components of the ECM, induce an overactivation of the immune system. In this context, ECM represents an important player in inflammatory diseases, including the inflammatory bowel diseases (IBD) and related complications such as intestinal fibrosis. In the last years, progressive advancements in the knowledge of IBD pathogenesis have provided crucial information for the discovery of new treatments. Nevertheless, few studies investigate the ECM's multiple roles in the sustenance and the exacerbation of the immune reaction.

This review aims to emphasize the dynamic aspects of the ECM, giving an overview of its direct involvement in intestinal inflammatory diseases and the related intestinal fibrosis.