Molecular Basis of Intestinal Fibrosis in Inflammatory Bowel Disease

Abstract

Background: Intestinal fibrosis in Crohn's disease (CD) is considered to be irreversible and induces persistent luminal narrowing and strictures. In the past decades, substantial advances have been made in the understanding of the cellular and molecular mechanisms underlying intestinal fibrosis in inflammatory bowel disease (IBD).

Summary: Intestinal fibrosis is typically associated with mesenchymal cell hyperplasia, tissue disorganization, and deposition of extracellular matrix (ECM). The transient appearance of mesenchymal cells is a feature of normal wound healing, but the persistence of these cells is associated with ECM deposition and fibrosis, leading to loss of normal architecture and function. When homeostatic control of the repair process becomes dysregulated, perpetual activation of profibrotic responses and sustained accumulation of ECM are induced. In the process of intestinal fibrosis, myofibroblasts are considered to be the key effector cells, being responsible for the synthesis of ECM proteins. Activation and accumulation of myofibroblasts in the stricturing lesions of CD patients are mediated by various factors such as growth factors, cytokines, epithelial-to-mesenchymal or endothelial-to-mesenchymal transitions. Despite the identification of many putative targets and target pathways applicable to antifibrotic therapies, no such treatment has yet been successful. Predictive biomarkers and non-invasive diagnostic tools for intestinal fibrosis are still insufficient in IBD.

Key message: We summarize recent advances in the understanding of the cellular and molecular mechanisms underlying intestinal fibrosis in IBD.

Keywords: Antifibrotic therapy; Epithelial-to-mesenchymal transition; Intestinal myofibroblasts; Transforming growth factor-β.