B3GNT7 regulates mucin O-glycosylation to alleviate colonic inflammation
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ABSTRACT:
PROVIDER: PRJNA1022493 | ENA |
REPOSITORIES: ENA
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Project description:B3GNT7, an important glycosyltransferase highly expressed in intestinal epithelial cells, is involved in physiological processes in the intestine. This study presents novel findings on the potential role and mechanism of B3GNT7 in ulcerative colitis (UC). DSS-induced mouse model of colitis was established to investigate the expression of B3GNT7 in the colon using transcriptomics and immunohistochemistry. Bioinformatics analysis was conducted to explore the biological functions of B3GNT7. The correlation between the transcription levels of B3GNT7 in the colonic tissues of UC patients from the IBDMDB database was analyzed and the severity of colonic inflammation, along with potential mechanisms. The DSS-induced colitis mouse model was successfully established, and transcriptomic analysis revealed a significant downregulation of B3GNT7 expression in the colonic tissues compared to healthy mice. Functional enrichment analysis showed that the main biological function of B3GNT7 was to participate in the mucin O-glycosylation process. Protein interaction analysis indicates that the molecules showing strong interaction with B3GNT7 were members of the mucin MUC family, including MUC2, MUC3, and MUC6. In UC patients, the transcription levels of B3GNT7 were significantly decreased, particularly in patients with moderate to severe disease activity. The expression level of B3GNT7 was negatively correlated with the endoscopic severity of UC. Gene set enrichment analysis (GSEA) further revealed significant enrichment of B3GNT7 in the mucin O-glycosylation synthesis signaling pathway. The downregulation of B3GNT7 expression in the colonic tissues of UC may contribute to impaired mucin barrier function and the progression of colitis.
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Project description:Aberrant mucin type O-linked glycosylation is a common occurrence in cancer. This type of O-linked glycosylation can occur on many cell surface glycoproteins where only a small number of sites may be present. EGFR is one such glycoprotein. Upon EGF ligation, EGFR induces a signaling cascade but can also translocate to the nucleus where it can directly regulate gene transcription. Here we show that upon EGF binding, breast cancer cells carrying different O-linked glycans respond by transcribing differential gene expression signatures. This is not a result of changes in signal transduction but due to the differential nuclear translocation of EGFR in the two glyco-phenotypes. This appears to be regulated by the formation of a EGFR/galectin-3/MUC1 complex at the cell surface that is present in cells carrying short core1-based O-glycans characteristic of tumour cells but absent in core 2 O-glycan carrying cells representative of normal mammary epithelial cells.
2020-12-04 | GSE107629 | GEO
Project description:Damage of the intestinal epithelial barrier by xenobiotics or reactive oxygen species and a dysregulated immune response are both factors involved in the pathogenesis of inflammatory bowel diseases (IBD). Curcumin and rutin are polyphenolic compounds known to have anti-oxidant and anti-inflammatory activities, but their mechanism(s) of action are yet to be fully elucidated. Mdr1a-/- mice spontaneously develop intestinal inflammation, predominantly in the colon, with pathology similar to IBD, so this mouse model is relevant for studying diet-gene interactions and potential effects of foods on remission or development of IBD. This study tested whether the addition of curcumin or rutin to the diet would alleviate colonic inflammation in mdr1a-/- mice. Using whole-genome microarrays, the effect of dietary curcumin on gene expression in colon tissue was also investigated. Twelve mice were randomly assigned to each of three diets; control (AIN-76A), control + 0.2% curcumin or control + 0.1% rutin and monitored from the age of 7 to 24 weeks. Curcumin, but not rutin, significantly reduced histological signs of colonic inflammation in mdr1a-/- mice. Microarray and pathway analyses suggested that the effect of dietary curcumin on colon inflammation could be via an up-regulation of xenobiotic metabolism and a down-regulation of pro-inflammatory pathways probably mediated by PXR and PPARï¡ activation of RXR. These results reveal the potential of global gene expression and pathway analyses to study and better understand the effect of foods in colonic inflammation. Experiment Overall Design: Twelve mice were randomly assigned to each of three diets; control (AIN-76A), control + 0â¢2% curcumin or control + 0â¢1% rutin and monitored from the age of 7 to 24 weeks. As only curcumin significantly reduced colonic HIS, comparison of the gene expression levels in colon was carried out using total RNA from colon tissue of four mdr1a-/- mice from the control group (high HIS) and four mdr1a-/- mice from the curcumin group (low HIS). A reference design with eight arrays was used for this comparison, where each individual RNA sample was hybridized in the array with the reference RNA, totalizing 4 biological replicates per treatment.
2008-06-11 | E-GEOD-10684 | biostudies-arrayexpress
Project description:Intestinal epithelia are protected by a layer of mucin secreted by goblet cells against mechanical and chemical injuries, potent causes of inflammation, and the most abundant secreted intestinal mucin is encoded by the Muc2 gene. Genetic deletion of Muc2 causes intestinal inflammation in early stage and tumors after 3 months. The underlying mechanisms are not clear, but epigenetic alterations, particularly, up- and down-regulated microRNAs are involved in the malignant transformation from colitis to cancer. We used miRNA array to profile the differential expression of the miRNAs in Muc2-/- mouse colonic epithelial lin comparison with those in wild-type mice. Total RNA were extracted from mouse colonic epithelial cells and Muc2-/- and +/+, and the RNA were hybridized on Affymetrix miRNA microarray to determine the alterations of miRNAs during colitis development and its malignant transformation from colitis to cancer. To the end, we found miRNA were differential expressed in the Muc2-/- mice, among them 20 miRNAs were significantly downregulated and 71 miRNAs were significantly upregulated in Muc2-/- mice, in comparison with Muc2+/+ mice (change fold >2 or <0.5; T<0.01, p value< 0.05, q value< 0.05).
2014-05-31 | E-GEOD-56577 | biostudies-arrayexpress
Project description:Intestinal epithelia are protected by a layer of mucin secreted by goblet cells against mechanical and chemical injuries, potent causes of inflammation, and the most abundant secreted intestinal mucin is encoded by the Muc2 gene. Genetic deletion of Muc2 causes intestinal inflammation in early stage and tumors after 3 months. The underlying mechanisms are not clear, but epigenetic alterations, particularly, up- and down-regulated microRNAs are involved in the malignant transformation from colitis to cancer. We used miRNA array to profile the differential expression of the miRNAs in Muc2-/- mouse colonic epithelial lin comparison with those in wild-type mice.
2014-05-31 | GSE56577 | GEO
Project description:Damage of the intestinal epithelial barrier by xenobiotics or reactive oxygen species and a dysregulated immune response are both factors involved in the pathogenesis of inflammatory bowel diseases (IBD). Curcumin and rutin are polyphenolic compounds known to have anti-oxidant and anti-inflammatory activities, but their mechanism(s) of action are yet to be fully elucidated. Mdr1a-/- mice spontaneously develop intestinal inflammation, predominantly in the colon, with pathology similar to IBD, so this mouse model is relevant for studying diet-gene interactions and potential effects of foods on remission or development of IBD. This study tested whether the addition of curcumin or rutin to the diet would alleviate colonic inflammation in mdr1a-/- mice. Using whole-genome microarrays, the effect of dietary curcumin on gene expression in colon tissue was also investigated. Twelve mice were randomly assigned to each of three diets; control (AIN-76A), control + 0.2% curcumin or control + 0.1% rutin and monitored from the age of 7 to 24 weeks. Curcumin, but not rutin, significantly reduced histological signs of colonic inflammation in mdr1a-/- mice. Microarray and pathway analyses suggested that the effect of dietary curcumin on colon inflammation could be via an up-regulation of xenobiotic metabolism and a down-regulation of pro-inflammatory pathways probably mediated by PXR and PPARalpha activation of RXR. These results reveal the potential of global gene expression and pathway analyses to study and better understand the effect of foods in colonic inflammation. Keywords: Colonic inflammation, gene expression, curcumin, rutin, genome-wide microarrays
2008-04-10 | GSE10684 | GEO
Project description:Background: Ulcerative colitis (UC) develops from chronic inflammation of the colon. Most patients respond favorably to medical management, however around 25% of UC patients will require surgery to treat their disease. While surgery is the only curative treatment for UC, it can carry its own risks, particularly when the surgery is emergent. Time from diagnosis to surgery varies dramatically amongst UC patients, thus a better understanding of how the colonic microenvironment relates to disease severity is needed to improve patient outcomes. Methods: We conducted RNA-seq on full-thickness sigmoid colonic tissues from 26 UC patients undergoing colectomy for their disease. Hierarchical clustering of the transcriptomes identified disease subsets. Subsets were characterized using differential gene expression analysis, cell type deconvolution, and network analysis. Results: We identified two distinct UC subsets in our cohort that were distinguished by 957 differentially expressed genes. Cluster 1 was enriched in genes associated with intestinal epithelial cell differentiation, while cluster 2 was enriched in genes associated with epithelial-to-mesenchymal transition and inflammatory responses. Cluster 1 was associated with an extended time from UC diagnosis to colectomy. Of cluster 1 genes, elevated MUC5B, MUC4, and MUC2 expression displayed the strongest correlation with increased time to surgery. Conclusion: Our transcriptome analysis indicates that UC can be subclassified into at least two distinct molecular signatures. We find that elevated mucin gene expression correlates with prolonged time to colectomy after diagnosis. These results identified MUC5B, MUC4, and MUC2 as potential prognostic indicators of disease severity, as reflected in time to surgery.
2020-04-18 | GSE130038 | GEO
Project description:The human gut microbiota is crucial for degrading dietary fibres from the diet. However, some of these bacteria can also degrade host glycans, such as mucins, the main component of the protective gut mucus layer. Specific microbiota species and mucin degradation patterns are associated with inflammatory processes in the colon. Yet, it remains unclear how the utilization of mucin glycans affects the degradation of dietary fibres by the human microbiota. Here, we used three dietary fibres (apple pectin, β-glucan and xylan) to study in vitro the dynamics of colon mucin and dietary fibre degradation by the human faecal microbiota. The dietary fibres showed clearly distinguishing modulatory effects on faecal microbiota composition. The utilization of colon mucin in cultures led to alterations in microbiota composition and metabolites. Metaproteome analysis showed the central role of the Bacteroides in degradation of complex fibres while Akkermansia muciniphila was the main degrader of colonic mucin. This work demonstrates the intricacy of complex glycan metabolism by the gut microbiota and how the utilization of host glycans leads to alterations in the metabolism of dietary fibres. Metaproteomics analysis of this data reveals the functional activities of the bacteria in consortia, by this contributing to a better understanding of the complex metabolic pathways within the human microbiota that can be manipulated to maximise beneficial microbiota-host interactions. In this study two different mucin samples were used: commercial porcine gastric mucin and in house prepared porcine colonic mucin. This dataset analyses the proteome of: A) autoclaved porcine colonic mucin; B) not autoclaved porcine colonic mucin; C) porcine gastric mucin.
2024-06-13 | PXD036037 | Pride