High-Resolution Gene Expression Profiling Using RNA Sequencing in Patients With Inflammatory Bowel Disease and in Mouse Models of Colitis

Holgersen, Kristine; Kutlu, Burak; Fox, Brian; Serikawa, Kyle; Lord, James D.; Hansen, Axel Kornerup; Holm, Thomas Lindebo

doi:10.1093/ecco-jcc/jjv050

Cited by 61 publications

(70 citation statements)

References 79 publications

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“…Given that the PanCancer Immune Profiling probe set captures expression data for up to 750 genes, we sought to compare the transcriptional profiles for our TWD-exposed mice during colitis to other available datasets in animal models and human UC patients. Our comparison focused primarily on those studies using genome-wide methodologies including a genome-wide microarray study of mouse colon mucosa collected after 6 days exposure to 3% DSS [66], RNAseq analysis of colon mucosa collected after exposure to 4% DSS (5 days treatment, with collection on day 8) [67], RNAseq analysis of colon mucosa from the PAC-Il10 -/mouse model compared to wildtype [67], a microarray study of colon tissue samples from human UC patients compared to healthy controls [68], and an RNAseq assessment of colon tissues from human UC patients versus healthy controls [67]. (We note that other reports also employed genome-wide analyses to examine the colon transcriptome in DSS or IL-deficient mice, although the complete results or underlying data were not publicly available for us to use in this comparative analysis).…”

Section: Discussionmentioning

confidence: 99%

Consumption of the Total Western Diet Promotes Colitis and Inflammation-Associated Colorectal Cancer in Mice

et al. 2020

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Consumption of a Western type diet is a known risk factor for colorectal cancer. Our group previously developed the total Western diet (TWD) for rodents with energy and nutrient profiles that emulate a typical Western diet. In this study, we tested the hypothesis that consumption of the TWD would enhance colitis, delay recovery from gut injury and promote colon tumorigenesis.In multiple experiments using the azoxymethane + dextran sodium sulfate or Apc Min/+ mouse models of colitis-associated colorectal carcinogenesis (CAC), we determined that mice fed TWD experienced more severe and more prolonged colitis compared to their counterparts fed the standard AIN93G diet, ultimately leading to markedly enhanced colon tumorigenesis. Additionally, this increased tumor response was attributed to the micronutrient fraction of the TWD, and restoration of calcium and vitamin D to standard amounts ameliorated the tumor-promoting effects of TWD. Finally, exposure to the TWD elicited large scale, dynamic changes in mRNA signatures of colon mucosa associated with interferon (IFN) response, inflammation, innate immunity, adaptive immunity, and antigen processing pathways, among others. Taken together, these observations indicate that consumption of the TWD markedly enhanced colitis, delayed recovery from gut injury, and enhanced colon tumorigenesis likely via extensive changes in expression of immune-related genes in the colon mucosa.Nutrients 2020, 12, 544 2 of 35 characterizes these conditions is now recognized as an important factor in CRC due to its involvement in the disruption of the same oncogenic pathways that are disrupted in CRC [5]. The mutation of genes involved in the maintenance of the intestinal mucosal barrier that protects the intestinal wall from bacterial invasion contributes to both Crohn's and UC [6,7].Dysfunction of the intestinal mucosal barrier leads to sustained damage of gut epithelial cells. This chronic injury to the gut triggers a compensatory immune response characterized by the up-regulation of cell proliferation and anti-apoptotic pathways that promote cell survival [8]. Various molecules are involved in the activation of such pathways, including transcription factors (e.g., NF-κB, and STAT3) and various inflammatory cytokines (e.g., IL-6 and TNF-α), which are normally secreted during an inflammatory response. The resulting compensatory cell regeneration results in increased rates of mitosis that, when chronically active, increase DNA mutation rates [8,9]. Not only can this process promote the disruption of oncogenic pathways, but it can also provide cancerous cells with a nurturing environment due to the increased availability of proliferative and survival signals. This notion is supported by an animal study by Tanaka et al. [10], in which a combined treatment of the chemical carcinogen azoxymethane (AOM) with the inflammatory agent dextran sodium sulfate (DSS) significantly increased intestinal tumorigenesis in CD-1 mice. The AOM + DSS model yields a consistent, reproducible colon cancer outcome ...

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Section: Discussionmentioning

confidence: 99%

Consumption of the Total Western Diet Promotes Colitis and Inflammation-Associated Colorectal Cancer in Mice

et al. 2020

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“…Therefore, we expected to observe upregulation of collagen proteins and hydroxyproline-containing peptides. Indeed, increases in collagen transcripts were found with all 3 previously published transcriptomics datasets (28,30,58).…”

Section: Discussionmentioning

confidence: 60%

“Degradation of the extracellular matrix is part of the pathology of ulcerative colitis”

Kirov

Sasson

Zhang

et al. 2018

Preprint

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The scientific value of re-analyzing existing datasets is often proportional to the complexity of the data. Proteomics data are inherently complex and can be analyzed at many levels, including proteins, peptides, and post-translational modifications to verify and/or develop new hypotheses. In this paper, we present our re-analysis of a previously published study comparing colon biopsy samples from ulcerative colitis (UC) patients to non-affected controls. In addition to confirming and reinforcing the original finding of upregulation of neutrophil extracellular traps (NETs), we report novel findings, including that Extracellular Matrix (ECM) degradation and neutrophil maturation are involved in the pathology of UC.The pharmaceutically most relevant differential protein expressions were confirmed using immunohistochemistry as an orthogonal method. As part of this study, we also compared proteomics data to previously published mRNA expression data. These comparisons indicated compensatory regulation at transcription levels of the ECM proteins we identified and open possible new venues for drug discovery.

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“…RNA sequencing has been used to identify genomic mutations such as fusion transcripts in colon cancer[14], as well as the pathogenesis of colorectal cancer[15,16]. Attempts to discover a unique transcript marker for colorectal cancer[17,18] and inflammatory bowel disease have also been attempted for quicker diagnosis than current screening methods[19,20]. RNA sequencing has also been used to investigate treatment response for rectal cancer[21].…”

Section: Colorectal Disease and Rna Sequencingmentioning

confidence: 99%

High throughput RNA sequencing utility for diagnosis and prognosis in colon diseases

Gao

Zhong

Patel

et al. 2017

WJG

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RNA sequencing is the use of high throughput next generation sequencing technology to survey, characterize, and quantify the transcriptome of a genome. RNA sequencing has been used to analyze the pathogenesis of several malignancies such melanoma, lung cancer, and colorectal cancer. RNA sequencing can identify differential expression of genes (DEG’s), mutated genes, fusion genes, and gene isoforms in disease states. RNA sequencing has been used in the investigation of several colorectal diseases such as colorectal cancer, inflammatory bowel disease (ulcerative colitis and Crohn’s disease), and irritable bowel syndrome.

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High-Resolution Gene Expression Profiling Using RNA Sequencing in Patients With Inflammatory Bowel Disease and in Mouse Models of Colitis

Cited by 61 publications

References 79 publications

Consumption of the Total Western Diet Promotes Colitis and Inflammation-Associated Colorectal Cancer in Mice

Consumption of the Total Western Diet Promotes Colitis and Inflammation-Associated Colorectal Cancer in Mice

“Degradation of the extracellular matrix is part of the pathology of ulcerative colitis”

High throughput RNA sequencing utility for diagnosis and prognosis in colon diseases

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