Skip Navigation LinksHome > July 2014 - Volume 20 - Issue 7 > Mechanisms That Mediate the Development of Fibrosis in Patie...
Inflammatory Bowel Diseases:
doi: 10.1097/MIB.0000000000000043
Basic Science Review Articles

Mechanisms That Mediate the Development of Fibrosis in Patients With Crohn's Disease

Li, Chao MS, MD*; Kuemmerle, John F. MD*,†,‡

Collapse Box

Abstract

Crohn's disease is complicated by the development of fibrosis and stricture in approximately 30% to 50% of patients over time. The pathogenesis of fibrostenotic disease is multifactorial involving the activation of mesenchymal cells by cytokines, growth factors, and other mediators released by immune cells, epithelial cells, and mesenchymal cells. Transforming growth factor β, a key activator of mesenchymal cells, is central to the process of fibrosis and regulates numerous genes involved in the disordered wound healing including collagens, and other extracellular matrix proteins, connective tissue growth factor, and insulin-like growth factors. The activated mesenchymal compartment is expanded by recruitment of new mesenchymal cells through epithelial to mesenchymal transition, endothelial to mesenchymal transition, and invasion of circulating fibrocytes. Cellular hyperplasia and increased extracellular matrix production, particularly collagens, from fibroblasts, myofibroblasts, and smooth muscle cells add to the disturbed architecture and scarring on the intestine. Extracellular matrix homeostasis is further disrupted by alterations in the expression of matrix metalloproteinases and tissue inhibitors of metalloproteinase in the gut. Among the 163 susceptibility genes identified that contribute to susceptibility in inflammatory bowel disease mutations in NOD2/CARD15, innate immune system components and autophagy jointly contribute to the activation of mesenchymal cells and pathogenesis of fibrosis in this polygenic disorder. Numerous growth factors cytokines and other mediators also contribute to development of fibrosis in the susceptible patient. This review focuses on the molecular mechanisms that regulate mesenchymal cell function, particularly smooth muscle cells, the largest compartment of mesenchyme in the intestine, that lead to fibrosis in Crohn's disease.

Copyright © 2014 Crohn's & Colitis Foundation of America, Inc.

You currently do not have access to this article.

You may need to:

Note: If your society membership provides for full-access to this article, you may need to login on your society’s web site first.

Login

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.