Pathogenesis of fibrostenosing Crohn's disease

Crohn's disease (CD) is a chronic inflammatory disease, which could affect any part of the gastrointestinal tract. A severe complication of CD is fibrosis-associated strictures, which can cause bowel obstruction. Unfortunately, there is no specific antifibrotic therapy available. More than 80% of the patients with CD will have to undergo at least 1 surgery in their life and recurrence of strictures after surgery is common. Investigations on the mechanism of fibrostenosing CD have revealed that fibrosis is mainly driven by expansion of mesenchymal cells including fibroblasts, myofibroblasts, and smooth muscle cells. Being exposed to a pro-fibrotic milieu, these cells increase the secretion of extracellular matrix, as well as crosslinking enzymes, which drive tissue stiffness and remodeling. Fibrogenesis can become independent of inflammation in later stages of disease, which offers unique therapeutic potential. Exciting new evidence suggests smooth muscle cell hyperplasia as a strong contributor to luminal narrowing in fibrostenotic CD. Approval of new drugs in other fibrotic diseases, such as idiopathic pulmonary fibrosis, as well as new targets associated with fibrosis found in CD, such as cadherins or specific integrins, shed light on the development of novel antifibrotic approaches in CD.