The Pathogenesis and Clinical Management of Stricturing Crohn Disease

Schmoyer, Christopher J.; Saidman, Jakob; Bohl, Jaime L.; Bierly, Claire L; Kuemmerle, John F.; Bickston, Stephen J.

doi:10.1093/ibd/izab038

Cited by 12 publications

(10 citation statements)

References 118 publications

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“… 44 However, the underlying mechanisms through which NOD2 drives fibrosis formation remain elusive. 6 Nayar et al 45 first unveiled how NOD2 deficiencies predisposed CD patients to develop a stricturing phenotype [ Figure 2(e) ]. They defined a unique activated fibroblast population characterized by CD14 and PDGFRA expression via single-cell RNA sequencing of inflamed ileum from patients with CD.…”

Section: Search Strategymentioning

confidence: 99%

“… 5 However, they are not ideal due to a high rate of postoperative recurrence and complications. 6 To date, there are still no licensed antifibrotic agents, 7 partly due to the poor understanding of the mechanisms of initiation and propagation of intestinal fibrosis. Specific predictors that are capable of identifying CD patients at a high risk of developing strictures are also lacking, which may account for the lack of timely treatment.…”

Section: Introductionmentioning

confidence: 99%

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Intestinal strictures in Crohn’s disease: a 2021 update

Lin

Wang

Liu

et al. 2022

Therap Adv Gastroenterol

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Intestinal strictures remain one of the most intractable and common complications of Crohn’s disease (CD). Approximately 70% of CD patients will develop fibrotic strictures after 10 years of CD diagnosis. Since specific antifibrotic therapies are unavailable, endoscopic balloon dilation and surgery remain the mainstay treatments despite a high recurrence rate. Besides, there are no reliable methods for accurately evaluating intestinal fibrosis. This is largely due to the fact that the mechanisms of initiation and propagation of intestinal fibrosis are poorly understood. There is growing evidence implying that the pathogenesis of stricturing CD involves the intricate interplay of factors including aberrant immune and nonimmune responses, host-microbiome dysbiosis, and genetic susceptibility. Currently, the progress on intestinal strictures has been fueled by the advent of novel techniques, such as single-cell sequencing, multi-omics, and artificial intelligence. Here, we perform a timely and comprehensive review of the substantial advances in intestinal strictures in 2021, aiming to provide prompt information regarding fibrosis and set the stage for the improvement of diagnosis, treatment, and prognosis of intestinal strictures.

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Section: Search Strategymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Intestinal strictures in Crohn’s disease: a 2021 update

Lin

Wang

Liu

et al. 2022

Therap Adv Gastroenterol

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“…Хронічне запалення, численні виразки та пошкодження стінок кишечника можуть викликати неконтрольоване відкладання позаклітинного матриксу (ПКМ) та бути причиною розвитку фібротичних змін [4,5], оскільки основними компонентами ПКМ є фібронектин, колагени, ламініни та протеоглікани [6,7,18]. Тому основні ускладнення при ХК, що можуть вимагати хірургічного втручання, включають утворення фіброзних стриктур, нориць, зниження всмоктувальної функції, ризик розвитку раку.…”

Section: вступunclassified

Histo- and morphometric changes in the large intestine mucosa in Crohn’s disease depending on the presence of fibrosis

Gaydar¹,

Stoykevich²,

Mylostуva³

et al. 2022

GASTRO

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Background. One of the common complications of Crohn’s disease is the development of fibrotic changes in the wall of the large intestine, and, as a result, the risk of strictures. Morphometric study of the cellular composition of large intestine biopsy samples is one of the extended links of the diagnostic criteria for inflammatory bowel diseases, which make it possible to predict the development of the disease. Changes in the number of fibroblasts, as components of mesenchymal cells, can be considered a protective reaction to the intestinal tissue damage. The purpose of the study was to reveal changes in the histo- and morphometric parameters of the large intestine mucosa depending on the development of intestinal fibrosis in Crohn’s disease. Materials and methods. Colon biopsy samples from patients with Crohn’s disease (n = 38) were examined histologically and morphometrically. According to morphological studies, patients were divided into two groups: with fibrotic changes in the intestinal wall (n = 10) and without fibrosis (n = 28). Results. Histologically, changes in the intestinal mucosa were observed in the form of altered integrity of the epithelium (78.3 %), crypt architectonics (34.2 %), mucosal edema (28.9 %), crypt abscesses (47.3 %). Fibrotic changes of the intestinal mucosa were found in 26.3 % of patients. The inflammatory infiltrate contained neutrophils, eosinophils, lymphocytes, plasma cells, fibrocytes, and macrophages. At the same time, in the group of patients with Crohn’s disease and fibrosis, the number of representatives of the inflammatory infiltrate was higher than in the group of patients with Crohn’s disease without fibrosis. Patients with fibrotic changes in the intestinal wall were characterized by a higher density of inflammatory infiltrate the composition of which was dominated by macrophages and fibroblasts. Thickening of the intestinal mucosa was also observed in patients with fibrosis. The cause for such changes is the activation of the mechanism of fibrosis development against the background of inflammatory processes. Direct correlations were found between the fibrosis of the colon wall and the depth of crypts (r = 0.35; p < 0.05), the height of the crypt epithelium (r = 0.41; p < 0.05), cellular density of the infiltrate (r = 0.45; p < 0.05), the number of neutrophils (r = 0.47; p < 0.05), eosinophils (r = 0.39; p < 0.05), fibroblasts (r = 0.57; p < 0.05). Conclusions. In colon biopsy samples of patients with Crohn’s disease and intestinal fibrosis, a denser and increased level of inflammatory infiltrate is noted. The active development of the fibrotic process is directly related to the high level of fibroblasts in the infiltrate.

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Section: Introductionmentioning

confidence: 99%

“…Crohn's disease (CD) is characterized by chronic and relapsing intestinal inflammation, and hypertrophy of mesenteric adipose tissue (MAT) enveloping the lesions in the intestine. 1 , 2 , 3 The crosstalk between MAT and the intestine affects the progression of CD. 4 Studies have shown that the MAT in CD exhibits endocrine and metabolic dysfunction, 5 as well as poor differentiation, 6 and little is known about the underlying mechanism.…”

Section: Introductionmentioning

confidence: 99%

Pygopus2 ameliorates mesenteric adipocyte poor differentiation to alleviate Crohn's disease ‐like colitis via the Axin2/GSK3β pathway

Zuo

Geng

et al. 2022

Cell Proliferation

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Objectives: Crohn's disease (CD) mesenteric adipose tissue (MAT) inflammation affects enteritis through the interaction between the mesentery and intestine, and we previously found that poorly differentiated mesenteric adipocytes were related to its inflammatory features. Pygopus2 (Pygo2) is a key negative regulator of adipocyte differentiation. We aimed to determine whether Pygo2 participates in CD mesenteric lesions and whether Pygo2 knockdown would be beneficial in a CD model (Il-10 À/À mice).Methods: Pygo2 expression in MAT from control and CD patients and Il-10 À/À mice was measured by immunohistochemistry. Lentiviral transfection was used to regulate Pygo2 expression in Il-10 À/À mice, and the effects on mesenteric adipocyte differentiation, inflammation, and dysfunction during spontaneous colitis, as well as the possible mechanism, were investigated.Results: Pygo2 expression was increased in MAT from CD patients and Il-10 À/À mice, and its expression correlated with poor adipocyte differentiation and inflammation.Pygo2 knockdown significantly ameliorated colitis in Il-10 À/À mice. Moreover, the downregulation of Pygo2 gene expression could promote adipocyte differentiation and inhibit adipocyte inflammation in vivo and in vitro, and the effects were at least partly mediated by the Axis inhibition protein 2 (Axin2)/glycogen synthase kinase 3 beta (GSK3β) pathway. Conclusions:The increase in Pygo2 may be related to mesenteric adipocyte poor differentiation and inflammatory features of CD, and Pygo2 inhibition could alleviate CD-like colitis by improving mesenteric lesions by regulating the Axin2/GSK3β pathway.Jing Li and Lugen Zuo contributed equally to this work.

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The Pathogenesis and Clinical Management of Stricturing Crohn Disease

Cited by 12 publications

References 118 publications

Intestinal strictures in Crohn’s disease: a 2021 update

Intestinal strictures in Crohn’s disease: a 2021 update

Histo- and morphometric changes in the large intestine mucosa in Crohn’s disease depending on the presence of fibrosis

Pygopus2 ameliorates mesenteric adipocyte poor differentiation to alleviate Crohn's disease ‐like colitis via the Axin2/GSK3β pathway

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