AUTHOR=Hayashi Yuki , Nakase Hiroshi TITLE=The Molecular Mechanisms of Intestinal Inflammation and Fibrosis in Crohn’s Disease JOURNAL=Frontiers in Physiology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2022.845078 DOI=10.3389/fphys.2022.845078 ISSN=1664-042X 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.