Crohn’s Strictures—Moving Away from the Knife

Stenke, Emily; Bourke, Billy; Knaus, Ulla G.

doi:10.3389/fped.2017.00141

Cited by 15 publications

(9 citation statements)

References 88 publications

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“…Intestinal fibrosis is a common complication of IBD: almost 30% of patients with CD and 5% of patients with UC undergo surgery due to intestinal strictures, with a recurrence risk around 50% (21, 22). Intestinal stenosis is detected in approximately 10-17% of children at the diagnosis, affecting up to 40% by 10 years after diagnosis (23).…”

Section: Discussionmentioning

confidence: 99%

Transcription Factor ZNF281: A Novel Player in Intestinal Inflammation and Fibrosis

et al. 2018

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Background and aims: Recent evidences reveal the occurrence of a close relationship among epithelial to mesenchymal transition (EMT), chronic inflammation and fibrosis. ZNF281 is an EMT-inducing transcription factor (EMT-TF) involved in the regulation of pluripotency, stemness, and cancer. The aim of this study was to investigate in vitro, in vivo, and ex vivo a possible role of ZNF281 in the onset and progression of intestinal inflammation. A conceivable contribution of the protein to the development of intestinal fibrosis was also explored.Methods: Human colorectal adenocarcinoma cell line, HT29, and C57BL/6 mice were used for in vitro and in vivo studies. Mucosal biopsy specimens were taken during endoscopy from 29 pediatric patients with Crohn's disease (CD), 24 with ulcerative colitis (UC) and 16 controls. ZNF281 was knocked down by transfecting HT29 cells with 20 nM small interference RNA (siRNA) targeting ZNF281 (siZNF281).Results: We show for the first time that ZNF281 is induced upon treatment with inflammatory agents in HT29 cells, in cultured uninflamed colonic samples from CD patients and in DSS-treated mice. ZNF281 expression correlates with the disease severity degree of CD and UC patients. Silencing of ZNF281 strongly reduces both inflammatory (IL-8, IL-1beta, IL-17, IL-23) and EMT/fibrotic (SNAIL, Slug, TIMP-1, vimentin, fibronectin, and α-SMA) gene expression; besides, it abolishes the increase of extracellular-collagen level as well as the morphological modifications induced by inflammation.Conclusions: The identification of transcription factor ZNF281 as a novel player of intestinal inflammation and fibrosis allows a deeper comprehension of the pathogenetic mechanisms underlying inflammatory bowel disease (IBD) and provide a new target for their cure.

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Section: Discussionmentioning

confidence: 99%

Transcription Factor ZNF281: A Novel Player in Intestinal Inflammation and Fibrosis

et al. 2018

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“…Increased protease activity and degradation of the ECM in the intestinal mucosa and submucosa have been reported in both ulcerative colitis (UC) and Crohn's disease (CD) (6,(8)(9)(10)(11). Many IBD patients also suffer from intestinal fibrosis, which involves the accumulation of ECM components like collagen along the lining of the colonic epithelium (4, [12][13][14]. Excessive ECM degradation and deposition may result in the development of fistulae and strictures, respectively, with serious clinical consequences (15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

Inflammatory bowel disease-associated gut commensals degrade components of the extracellular matrix

Porras

Zhou

Shi

et al. 2022

Preprint

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Extracellular matrix (ECM) remodeling has emerged as a key feature of inflammatory bowel disease (IBD), and ECM fragments have been proposed as markers of clinical disease severity. Recent studies report increased protease activity in the gut microbiota of IBD patients. Nonetheless, the relationship between gut microbiota and ECM remodeling has remained unexplored. We hypothesized that members of the human gut microbiome can degrade host ECM, and that bacteria-driven remodeling, in turn, can enhance colonic inflammation. Through a variety of in vitro assays, we first confirmed that multiple bacterial species found in the human gut are capable of degrading specific ECM components. Clinical stool samples obtained from ulcerative colitis patients also exhibited higher levels of proteolytic activity in vitro compared to those of their healthy counterparts. Furthermore, culture supernatants from bacteria species capable of degrading human ECM accelerated inflammation in a dextran sodium sulfate (DSS)-induced colitis. Finally, we identified several of the bacterial proteases and carbohydrate degrading enzymes (CAZymes) potentially responsible for ECM degradation in vitro. Some of these protease families and CAZymes were also found in increased abundance in a metagenomic cohort of IBD. These results demonstrate that some commensal bacteria in the gut are indeed capable of degrading components of human ECM in vitro and suggest this proteolytic activity may be involved in the progression of IBD. A better understanding of the relationship between nonpathogenic gut microbes, host ECM, and inflammation could be crucial to unravel some of the mechanisms underlying host-bacteria interactions in IBD and beyond.

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“…Fibroblasts and myofibroblasts are the primary ECM producers, but emerging evidence points toward additional mechanisms of gut obstruction. In fact, thickening of the intestinal muscularis propria appears to be the major contributor to luminal narrowing and development of clinical symptoms 5 . In their lifetime, more than half of CD patients develop clinically apparent strictures, which are characterized on cross‐sectional imaging or histopathology by the presence of intestinal luminal narrowing, induced by bowel wall thickening 6 .…”

Section: Introductionmentioning

confidence: 99%

“…In fact, thickening of the intestinal muscularis propria appears to be the major contributor to luminal narrowing and development of clinical symptoms. 5 In their lifetime, more than half of CD patients develop clinically apparent strictures, which are characterized on cross-sectional imaging or histopathology by the presence of intestinal luminal narrowing, induced by bowel wall thickening. 6 However, in these population-based studies, diagnosis of strictures is mostly based on symptoms and likely underestimates the real incidence of fibrosis.…”

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confidence: 99%

Novel mechanisms and clinical trial endpoints in intestinal fibrosis*

Wang

Lin

Brown

et al. 2021

Immunological Reviews

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Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a relapsing inflammatory condition of the gastrointestinal tract. It has become a healthcare burden with the highest prevalence in Europe and North America, and accelerating incidence in Asia, Africa, and South America. 1 While UC is restricted to the colon with continuous superficial inflammation of the mucosa layer, CD can occur in both small and large intestine with patchy, transmural inflammation. 2 Intestinal fibrosis which results in obstruction and need for surgical interventions is a serious and common complication of CD. 3 Deposition of extracellular matrix (ECM)

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Crohn’s Strictures—Moving Away from the Knife

Cited by 15 publications

References 88 publications

Transcription Factor ZNF281: A Novel Player in Intestinal Inflammation and Fibrosis

Transcription Factor ZNF281: A Novel Player in Intestinal Inflammation and Fibrosis

Inflammatory bowel disease-associated gut commensals degrade components of the extracellular matrix

Novel mechanisms and clinical trial endpoints in intestinal fibrosis*

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