scholarly journals Intestinal mucosa-derived DNA methylation signatures in the penetrating intestinal mucosal lesions of Crohn’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuan Li ◽  
Zhiming Wang ◽  
Xiuwen Wu ◽  
Gefei Wang ◽  
Guosheng Gu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Extracellular Matrix ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Signaling Pathways ◽  
Intestinal Mucosa ◽  
Receptor Interaction ◽  
Positive Regulation ◽  
Mucosal Lesions

AbstractThe purpose of this study was to evaluate genome-wide DNA methylation changes in intestinal mucosa tissue of adult patients with Crohn's disease comprehensively. DNA methylation chip was used to analyze abnormal methylation sites among penetrating and non-penetrating intestinal mucosa tissue of Crohn's disease and normal intestinal mucosa tissue of healthy controls. Methylation abnormalities of different locus were verified by pyrosequencing and quantitative polymerase chain reaction. Differential DNA methylation sites were participated in the positive regulation of apoptosis and the positive regulation of IL-8 production and were enriched in signaling pathways related to inflammatory bowel disease and extracellular matrix receptor interaction signaling pathways. Correlation analysis showed that the methylation abnormalities of HLA-DRB1 (r = − 0.62, P < 0.001), MUC1 (r = − 0.45, P = 0.01), YPEL5 (r = − 0.55, P = 0.001) and CBLB (r = − 0.62, P < 0.001) were significantly negatively correlated with their relative expression levels. The degree of methylation abnormality of MUC1 was negatively correlated with the disease activity score of Crohn's disease (r = − 0.50, P = 0.01). Apoptosis, interleukin-8 production and abnormal extracellular matrix might be involved in the mechanism of penetrating intestinal mucosal lesions in Crohn's disease. The degree of abnormal methylation of MUC1 was negatively correlated with the disease activity of Crohn's disease.

scholarly journals Transcriptional and Molecular Pathways Activated in Mesenteric Adipose Tissue and Intestinal Mucosa of Crohn’s Disease Patients

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Andressa Coope ◽  
Lívia Bitencourt Pascoal ◽  
Francesca Aparecida Ramos da Silva ◽  
José Diego Botezelli ◽  
Maria de Lourdes Setsuko Ayrizono ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Signaling Pathways ◽  
Intestinal Mucosa ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Mesenteric Adipose Tissue ◽  
Immune Mediated ◽  
First Time

Crohn’s disease (CD) is a chronic inflammatory disorder, characterized by cytokine imbalance and transcription signaling pathways activation. In addition, the increase of mesenteric adipose tissue (MAT) near the affected intestinal area is a hallmark of CD. Therefore, we evaluated the transcription signaling pathways and cytokines expression in intestinal mucosa and MAT of active CD patients. Ten patients with ileocecal CD and eight with noninflammatory diseases were studied. The biopsies of intestinal mucosa and MAT were snap-frozen and protein expression was determined by immunoblotting. RNA levels were measured by qPCR. The pIkB/IkB ratio and TNFαlevel were significantly higher in intestinal mucosa of CD when compared to controls. However, STAT1 expression was similar between intestinal mucosa of CD and controls. Considering the MAT, the pIkB/IkB ratio was significantly lower and the anti-inflammatory cytokine IL10 was significantly higher in CD when compared to controls. Finally, the protein content of pSTAT1 was higher in MAT of CD compared to controls. These findings reinforce the predominance of the proinflammatory NF-kB pathway in CD intestinal mucosa. For the first time, we showed the activation of STAT1 pathway in MAT of CD patients, which may help to understand the physiopathology of this immune mediated disease.

scholarly journals Ulcerative colitis, Crohn’s disease, and irritable bowel syndrome have different profiles of extracellular matrix turnover, which also reflects disease activity in Crohn’s disease

PLoS ONE ◽  
2017 ◽  
Vol 12 (10) ◽  
pp. e0185855 ◽  
Author(s):  
Joachim Høg Mortensen ◽  
Tina Manon-Jensen ◽  
Michael Dam Jensen ◽  
Per Hägglund ◽  
Lone Gabriels Klinge ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Extracellular Matrix ◽  
Irritable Bowel Syndrome ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Irritable Bowel

P112 STUDY OF THE PROTEOMIC PROFILE IN PATIENTS WITH CROHN’S DISEASE, ITS CORRELATION WITH DIAGNOSIS AND DISEASE ACTIVITY

2018 ◽  
Vol 154 (1) ◽  
pp. S58
Author(s):  
Salah Badr El-Din ◽  
Ezzat Ahmed ◽  
Doaa Header ◽  
Pacint Moez ◽  
Mohamed Ibrahim
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Proteomic Profile

Localization and Activity of Inflammatory Bowel Disease Using 111ln Leukocyte Imaging

1988 ◽  
Vol 27 (03) ◽  
pp. 83-86 ◽  
Author(s):  
B. Briele ◽  
F. Wolf ◽  
H. J. Biersack ◽  
F. F. Knapp ◽  
A. Hotze
Keyword(s):  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Cell Uptake ◽  
Disease Extent ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Leukocyte Imaging

A prospective study was initiated to compare the clinically proven results concerning localization/extent and activity of inflammatory bowel diseases with those of 111ln-oxine leukocyte imaging. All patients studied were completely examined with barium enema x-ray, clinical and laboratory investigations, and endoscopy with histopathology. A total of 31 leukocyte scans were performed in 15 patients (12 with Crohn’s disease, 3 with ulcerative colitis). The scans were graded by comparing the cell uptake of a lesion (when present) and a bone marrow area providing a count ratio (CR). The inflammatory lesions were correctly localized on 26 leukocyte scans, and in 21 scans the scintigraphically estimated extent of disease was identical to endoscopy. In 5 cases the disease extent was underestimated, 4 scans in patients with relapse of Crohn’s disease were falsely negative, and in one patient with remission truly negative. The scintigraphically assessed disease activity was also in a good agreement with clinical disease activity based on histopathology in all cases. We conclude that leukocyte imaging provides valuable information about localization and activity of inflammatory bowel disease.

ACTIVATED INTESTINAL MUSCLE CELLS PROMOTE PREADIPOCYTE MIGRATION: A NOVEL MECHANISM OF CREEPING FAT FORMATION IN CROHN’S DISEASE

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S34-S34
Author(s):  
Ren Mao ◽  
Genevieve Doyon ◽  
Ilyssa Gordon ◽  
Jiannan Li ◽  
Sinan Lin ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Ex Vivo ◽  
Muscularis Propria ◽  
Dominant Factor ◽  
Stricture Formation ◽  
Intestinal Tissue ◽  
Mesenteric Fat

Abstract Background and Aims Creeping fat, the wrapping of mesenteric fat around the bowel wall, is a typical feature of Crohn’s disease, and is associated with stricture formation and bowel obstruction. How creeping fat forms is unknown, and we interrogated potential mechanisms using novel intestinal tissue and cell interaction systems. Methods Tissues from normal, ulcerative colitis, non-strictured and strictured Crohn’s disease intestinal specimens were obtained. Fresh and decellularized tissue, mesenteric fat explants, primary human adipocytes, pre-adipocytes, muscularis propria cells, and native extracellular matrix were used in multiple ex vivo and in vitro systems involving cell growth, differentiation and migration, proteomics, and integrin expression. Results Crohn’s disease muscularis propria cells produced an extracellular matrix scaffold which is in direct spatial and functional contact with the immediately overlaid creeping fat. The scaffold contained multiple proteins, but only fibronectin production was singularly upregulated by TGF-b1. The muscle cell-derived matrix triggered migration of pre-adipocytes out of mesenteric fat, fibronectin being the dominant factor responsible for their migration. Blockade of α5β1 on the pre-adipocyte surface inhibited their migration out of mesenteric fat and on 3D decellularized intestinal tissue extracellular matrix. Conclusion Crohn’s disease creeping fat appears to result from the migration of pre-adipocytes out of mesenteric fat and differentiation into adipocytes in response to an increased production of fibronectin by activated muscularis propria cells. These new mechanistic insights may lead to novel approaches for prevention of creeping fat-associated stricture formation.

scholarly journals Leucine-rich alpha-2 glycoprotein is a potential biomarker to monitor disease activity in inflammatory bowel disease receiving adalimumab: PLANET study

2021 ◽  
Author(s):  
Shinichiro Shinzaki ◽  
Katsuyoshi Matsuoka ◽  
Hiroki Tanaka ◽  
Fuminao Takeshima ◽  
Shingo Kato ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Fecal Calprotectin ◽  
Potential Biomarker ◽  
Adalimumab Therapy ◽  
Adalimumab Treatment ◽  
Inflammatory Bowel

Abstract Background This multicenter prospective study (UMIN000019958) aimed to evaluate the usefulness of serum leucin-rich alpha-2 glycoprotein (LRG) levels in monitoring disease activity in inflammatory bowel disease (IBD). Methods Patients with moderate-to-severe IBD initiated on adalimumab therapy were enrolled herein. Serum LRG, C-reactive protein (CRP), and fecal calprotectin (fCal) levels were measured at week 0, 12, 24, and 52. Colonoscopy was performed at week 0, 12, and 52 for ulcerative colitis (UC), and at week 0, 24, and 52 for Crohn’s disease (CD). Endoscopic activity was assessed using the Simple Endoscopic Score for Crohn’s Disease (SES-CD) for CD and the Mayo endoscopic subscore (MES) for UC. Results A total of 81 patients was enrolled. Serum LRG levels decreased along with improvements in clinical and endoscopic outcomes upon adalimumab treatment (27.4 ± 12.6 μg/ml at week 0, 15.5 ± 7.7 μg/ml at week 12, 15.7 ± 9.6 μg/ml at week 24, and 14.5 ± 6.8 μg/ml at week 52), being correlated with endoscopic activity at each time point (SES-CD: r = 0.391 at week 0, r = 0.563 at week 24, r = 0.697 at week 52; MES: r = 0.534 at week 0, r = 0.429 at week 12, r = 0.335 at week 52). Endoscopic activity better correlated with LRG compared to CRP and fCal on pooled analysis at all time points (SES-CD: LRG: r = 0.636, CRP: r = 0.402, fCal: r = 0.435; MES: LRG: r = 0.568, CRP: 0.389, fCal: r = 0.426). Conclusions Serum LRG is a useful biomarker of endoscopic activity both in CD and UC during the adalimumab treatment.

scholarly journals Relevance of monitoring transmural disease activity in patients with Crohn’s disease: current status and future perspectives

2021 ◽  
Vol 14 ◽  
pp. 175628482110066
Author(s):  
Rune Wilkens ◽  
Kerri L. Novak ◽  
Christian Maaser ◽  
Remo Panaccione ◽  
Torsten Kucharzik
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Symptom Control ◽  
Current Status ◽  
Clinical Relapse ◽  
Cross Sectional ◽  
Treatment Targets ◽  
Endoscopic Remission ◽  
Transmural Inflammation

Treatment targets of inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn’s disease (CD) have evolved over the last decade. Goals of therapy consisting of symptom control and steroid sparing have shifted to control of disease activity with endoscopic remission being an important endpoint. Unfortunately, this requires ileocolonoscopy, an invasive procedure. Biomarkers [C-reactive protein (CRP) and fecal calprotectin (FCP)] have emerged as surrogates for endoscopic remission and disease activity, but also have limitations. Despite this evolution, we must not lose sight that CD involves transmural inflammation, not fully appreciated with ileocolonoscopy. Therefore, transmural assessment of disease activity by cross-sectional imaging, in particular with magnetic resonance enterography (MRE) and intestinal ultrasonography (IUS), is vital to fully understand disease control. Bowel-wall thickness (BWT) is the cornerstone in assessment of transmural inflammation and BWT normalization, with or without bloodflow normalization, the key element demonstrating resolution of transmural inflammation, namely transmural healing (TH) or transmural remission (TR). In small studies, achievement of TR has been associated with improved long-term clinical outcomes, including reduced hospitalization, surgery, escalation of treatment, and a decrease in clinical relapse over endoscopic remission alone. This review will focus on the existing literature investigating the concept of TR or residual transmural disease and its relation to other existing treatment targets. Current data suggest that TR may be the next logical step in the evolution of treatment targets.

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