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Mediators in Crohn’s disease influence the gene expression profiles of mesenchymal progenitor cells differentiated into the osteoblastic lineage.

ABSTRACT: Crohn’s disease (CD) is associated with a higher prevalence of osteoporosis, a complication that is increasingly recognised as a significant cause of morbidity. Its pathogenesis is still controversial, but activity of CD is thought to be one contributing factor.

ORGANISM(S): Homo sapiens

PROVIDER: GSE20941 | GEO | 2012/03/16

SECONDARY ACCESSION(S): PRJNA124421

REPOSITORIES: GEO

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Mediators in Crohn's disease influence the gene expression profiles of mesenchymal progenitor cells differentiated into the osteoblastic lineage.

Project description:Crohn's disease (CD) is associated with a higher prevalence of osteoporosis, a complication that is increasingly recognised as a significant cause of morbidity. Its pathogenesis is still controversial, but activity of CD is thought to be one contributing factor. Two-Color DRLL-IS-Design [Landgrebe et.al 2004: Efficient two-sample designs for microarray experiments with biological replications. In Silico Biology 4] including 12 Arrays, osteoporosis samples from 4 mc patients, control samples from 3 mc patients without osteoporosis

2012-03-16 | E-GEOD-20941 | biostudies-arrayexpress

RNA-seq of nonstenotic and stenotic areas of patients with Crohn’s disease

Project description:Fibrostenotic disease is a common complication in Crohn’s disease (CD). We performed bulk RNA sequencing (n=16) of paired intestinal biopsies taken from nonstenotic and stenotic areas of patients with CD (n=8).

2023-04-26 | E-MTAB-12788 | biostudies-arrayexpress

Fibrosis associated changes detected in the proteome of surface epithelium overlying Crohn’s Disease Strictures

Project description:Background and aims: Intestinal fibrosis is a common complication of Crohn’s disease (CD). It is characterised by an excessive accumulation of fibroblasts differentiating into activated myofibroblasts secreting excessive extracellular matrix. The potential role of the intestinal epithelium in this fibrotic process remains poorly defined. Methods: A total of 113 CD and control subjects were studied. We performed a pilot proteomic study comparing the proteome of surface epithelium isolated by laser capture microdissection in normal and fibrotic zones of resected ileal CD strictures (n=5). Selected proteins were validated by immunohistochemistry (IHC) in colonic and ileal samples of stricturing CD patients (n=44), pure inflammatory CD (n=29) and control subjects (n=40). Functional assays with cell lines cultures and a fibroblast to myofibroblast differentiation model were used to assess the role of the highlighted epithelial proteins in CD fibrosis. Results: Proteomic study revealed an endoplasmic reticulum (ER) stress and unfolded protein response (UPR) markers increase in the epithelium overlying ileal fibrotic strictures, involving Anterior gradient protein 2 homolog (AGR2) and Binding immunoglobulin protein (BiP). This was confirmed by IHC. The ER stress induction in intestinal epithelial cells increased AGR2 as well as BiP expression and led to an extracellular secreted AGR2. A fibroblast to myofibroblast differentiation was obtained with the supernatant of intestinal epithelial cells pre-conditioned by ER stress and with recombinant AGR2. Conclusions: AGR2 and other ER stress markers are increased within the intestinal epithelium overlying fibrotic strictures and might contribute to profibrotic signals involved in CD fibrosis.

2022-04-04 | PXD022214 | Pride

The Gut Microbiota Metabolite Succinate promotes Adipose Tissue Browning in Crohn’s Disease

Project description:In Crohn’s disease (CD), microbe-host interactions are altered, with changes in microbial’s communities and barrier defects leading to translocation of microbes to surrounding adipose tissue (AT). We evaluated the presence of beige AT depots in CD and questioned whether succinate and/or bacterial translocation promotes white-to-beige transition in adipocytes.

2022-09-14 | PXD030520 | Pride

Assessing Cellular and Transcriptional diversity of IIeal Mucosa amongst Treatment Naïve and Treated Crohn’s disease

Project description:Crohn’s disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. We used single cell RNA sequencing (scRNAseq) to define the cellular and transcriptional activity of the mucosa at different stages of disease progression in CD.

2022-10-18 | GSE202052 | GEO

Single cell RNA-sequencing of cells isolated from full-thickness surgically resected tissue from stricturing and non-stricturing segments of the ileum of Crohn's disease patients

Project description:Intestinal fibrosis and stricture formation is an aggressive complication of Crohn’s disease (CD) and there is a clear unmet need for new therapies based on a better understanding of disease mechanisms. Knowledge of fibroblast heterogeneity is important as disease-state specific cell types represent important therapeutic targets. A lack of validated cell markers currently hampers progress.

2023-10-24 | E-MTAB-11792 | biostudies-arrayexpress

Multi-Omics Characterization of Colon Mucosa and Submucosa/Wall from Crohn’s Disease Patients

Project description:Crohn’s disease (CD) is a subtype of inflammatory bowel disease (IBD) characterized by transmural disease. The concept of transmural healing (TH) has been proposed as an indicator of deep clinical remission of CD and as a predictor of favorable treatment endpoints. Understanding the pathophysiology involved in transmural disease is critical to achieving these endpoints. How-ever, most studies have focused on the colon intestinal mucosa, overlooking the contribution of the colon intestinal wall in Crohn’s disease. Multi-omics approaches have provided new avenues for exploring the pathogenesis of Crohn’s disease and identifying potential biomarkers. Therefore, we analyzed and compared the gene and protein expression and dysregulated biological functions in the distinct tissue compartments of mucosa and submucosa/wall of colon resections from CD patients. We aimed to use transcriptomic and proteomic technologies to compare immune and mesenchymal cell profiles and pathways in the mucosal and submucosa/wall compartments to better understand refractory disease elements to achieve transmural healing. We employed a comprehensive multi-omics approach to investi-gate the molecular profiles of the colon mucosa and submucosa/wall compartments in patients with chronic Crohn’s disease. The results revealed similarities and differences in gene and protein ex-pression profiles, metabolic mechanisms, and immune and non-immune pathways between these two compartments. Additionally, the identification of protein isoforms highlights the complex molecular mechanisms underlying this disease. These findings have the potential to inform the development of novel therapeutic strategies to achieve TH.

2024-06-23 | PXD050335 | Pride

Etrolizumab-s fails to control E-Cadherin-dependent co-stimulation of highly stimulated cytotoxic T cells associated with Crohn’s disease

Project description:To interrogate the potential of αEβ7 integrin as a target in Crohn’s disease (CD), we single cell RNA-sequenced T cells from a patient with CD and a non-IBD control

2023-12-28 | GSE252122 | GEO

Integration of genome-wide DNA methylome and transcriptome of human intestinal fibroblasts reveals novel candidate gene signatures in Crohn’s disease-associated fibrosis

Project description:Tissue fibrosis is a serious complication of Crohn’s disease (CD) as well as of a variety of other complex, chronic pathologies. Understanding the underlying pathophysiology of tissue fibrosis is crucial for the development of tissue-specific prevention and interventional treatment strategies. To identify molecular states specific to fibrotic disease, we employed deep sequencing to define the genome-wide DNA methylome and the whole transcriptome of purified human intestinal fibrotic fibroblasts (HIFs) isolated from the colon of patients with fibrotic CD. Integration of this information, via computational tools, identified candidate molecular interactions that could lead to fibrosis pathology. Our definition of a genome-wide fibrosis-specific DNA methylome provides a new paradigm for understanding mechanisms of pathological gene expression that lead to intestinal fibrosis and may have relevance to fibrogenesis in other organs.

2016-03-22 | GSE67250 | GEO

Expression Profiles of Circular RNAs in colon biopsies from Crohn’s Disease Patients by Microarray Analysis

Project description:To investigate the expression profiles of circRNAs in colon tissues of the patients with Crohn’s Disease(CD) , ulcerative colitis (UC) and healthy controls (HC), we used circRNA microArray analysis form Arraystar to examine the expression of circRNAs in colon tissues of CD,UC and HC.

2019-05-30 | GSE131911 | GEO

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