Abstract
Crohn’s disease (CD) is an inflammatory bowel disease (IBD) with repeated remissions and relapses. As the disease progresses, fibrosis and narrowing of the intestine occur, leading to severe complications such as intestinal obstruction. Endoscopic balloon dilatation, surgical stricture plasty, and bowel resection have been performed to treat intestinal stenosis. The clinical issue is that some patients with CD have a recurrence of intestinal stenosis even after the medical treatments. On the other hand, there exist no established medical therapies to prevent stenosis. With the progressive intestinal inflammation, cytokines and growth factors, including transforming growth factor (TGF-β), stimulate intestinal myofibroblasts, contributing to fibrosis of the intestine, smooth muscle hypertrophy, and mesenteric fat hypertrophy. Therefore, chronically sustained inflammation has long been considered a cause of intestinal fibrosis and stenosis. Still, even after the advent of biologics and tighter control of inflammation, intestinal fibrosis’s surgical rate has not necessarily decreased. It is essential to elucidate the mechanisms involved in intestinal fibrosis in CD from a molecular biological level to overcome clinical issues. Recently, much attention has been paid to several key molecules of intestinal fibrosis: peroxisome proliferator-activating receptor gamma (PPARγ), toll-like receptor 4 (TLR4), adherent-invasive Escherichia coli (AIEC), Th17 immune response, and plasminogen activator inhibitor 1 (PAI-1). As a major problem in the treatment of CD, the pathophysiology of patients with CD is not the same and varies depending on each patient. It is necessary to integrate these key molecules for a better understanding of the mechanism of intestinal inflammation and fibrosis.
Highlights
Crohn’s disease (CD) is a chronic inflammatory bowel disease (IBD) that progresses irreversibly, with more than 30% of the patients gradually developing intestinal fibrosis, which leads to complications, such as intestinal obstruction, perforation, and fistula (Rieder et al, 2013)
In CD, even after the inflammation subsides, fibrosis progresses due to abnormal production of the fibrous matrix or reduced degradation of the matrix by the matrix metalloproteinase (MMP), both of which result in abnormal deposition of extracellular matrix (ECM) (Lawrance et al, 2001a; Speca et al, 2012)
There have been no studies regarding the relationship between PPARγ expression and microbiota composition in the intestines of IBD patients, disruption of gut microbiota can result in inappropriate PPARγ signaling responses in the intestinal epithelial cells, leading to further growth of the pathogenic gut bacteria and contributing to the exacerbation of ulcerative colitis (UC)
Summary
Crohn’s disease (CD) is a chronic inflammatory bowel disease (IBD) that progresses irreversibly, with more than 30% of the patients gradually developing intestinal fibrosis, which leads to complications, such as intestinal obstruction, perforation, and fistula (Rieder et al, 2013). The general mechanism of intestinal fibrosis is acute or chronic inflammation that leads. Cytokines and growth factors, such as transforming growth factor (TGF-β), stimulate the ECM component cells, namely the intestinal myofibroblasts (Bettenworth and Rieder, 2017). This results in excessive ECM re-synthesis, which, in turn leads to intestinal fibrosis. In the case of CD, chronic inflammation is the main factor leading to intestinal fibrosis.
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