Florian Rieder1, Claudio Fiocchi. 1. Department of Internal Medicine I, University of Regensburg, Regensburg, Germany; Department of Gastroenterology and Hepatology, Cleveland Clinic Foundation, Cleveland, USA; Department of Pathobiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, USA.
Abstract
BACKGROUND AND AIMS: Intestinal fibrosis is a common complication of IBD that can become seriously symptomatic and may require surgical intervention if stricture formation ensues. This review discusses existing and developing knowledge of intestinal fibrosis and its implications for therapy. METHODS: Review of the literature, personal communications, unpublished observations. RESULTS: Known mechanisms of intestinal fibrosis include fibroblast proliferation and migration, activation of stellate cells, and extraintestinal fibroblast recruitment. However, novel mechanisms are being uncovered, including epithelial-to-mesenchymal transition, endothelial-to-mesenchymal transition, pericyte differentiation, and fibrocyte recruitment. Most of the traditional and novel mechanisms underlying intestinal fibrosis are associated to the presence of chronic inflammation, but is also possible that fibrosis develops independently of persistent immune activation in the gut. At the moment, the development of preventive, non-interventional, and more effective management of intestinal fibrosis is hampered by the lack of a greater knowledge of its basic pathophysiology and predisposing factors. CONCLUSIONS: It is reasonable to expect that therapy of IBD-associated fibrosis will radically improve once the underlying mechanisms are better understood, and therapeutic modalities will emerge that prevent or reverse this complication of IBD.
BACKGROUND AND AIMS: Intestinal fibrosis is a common complication of IBD that can become seriously symptomatic and may require surgical intervention if stricture formation ensues. This review discusses existing and developing knowledge of intestinal fibrosis and its implications for therapy. METHODS: Review of the literature, personal communications, unpublished observations. RESULTS: Known mechanisms of intestinal fibrosis include fibroblast proliferation and migration, activation of stellate cells, and extraintestinal fibroblast recruitment. However, novel mechanisms are being uncovered, including epithelial-to-mesenchymal transition, endothelial-to-mesenchymal transition, pericyte differentiation, and fibrocyte recruitment. Most of the traditional and novel mechanisms underlying intestinal fibrosis are associated to the presence of chronic inflammation, but is also possible that fibrosis develops independently of persistent immune activation in the gut. At the moment, the development of preventive, non-interventional, and more effective management of intestinal fibrosis is hampered by the lack of a greater knowledge of its basic pathophysiology and predisposing factors. CONCLUSIONS: It is reasonable to expect that therapy of IBD-associated fibrosis will radically improve once the underlying mechanisms are better understood, and therapeutic modalities will emerge that prevent or reverse this complication of IBD.
Authors: Sarah K Daley; Marlys H Witte; Jalicia Washington; Michael Bernas; Pawel Kiela; Jennifer Thorn; Nathan Tanoue; J Steven Alexander Journal: Inflamm Bowel Dis Date: 2019-11-14 Impact factor: 5.325