Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1143454 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30175200_1.fastq.gz | Fastqsanger.gz | |||
| SRR30175300_1.fastq.gz | Fastqsanger.gz | |||
| SRR30175201_1.fastq.gz | Fastqsanger.gz | |||
| SRR30175301_1.fastq.gz | Fastqsanger.gz | |||
| SRR30175202_1.fastq.gz | Fastqsanger.gz |
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Project description:Background; MUC2 mucin produced by intestinal goblet cells is the major component of the intestinal mucus barrier. MUC2 homo-oligomerizes intracellularly into large secreted polymers which give mucus its viscous properties. The inflammatory bowel disease (IBD) ulcerative colitis is characterized by depleted goblet cells and a reduced mucus layer, whereas goblet cells and the mucus layer are increased in the other major inflammatory bowel disease, Crohnâs disease. Methods and Findings; By murine N-ethyl-N-nitrosourea-mutagenesis we identified two distinct non-complementing missense mutations in Muc2 exons encoding N- and C-terminal homo-oligomerization domains causing an ulcerative colitis-like phenotype. Both strains developed mild spontaneous distal intestinal inflammation, chronic diarrhea, rectal bleeding and prolapse, increased susceptibility to acute and chronic colitis induced by a luminal toxin, aberrant Muc2 biosynthesis, smaller goblet cell thecae (less stored mucin) and a diminished mucus barrier. Enhanced local production of IL-1beta, TNF-alpha and IFN-gamma was seen in the distal colon. The number of leukocytes within mesenteric lymph nodes was increased five-fold and leukocytes cultured in vitro produced both Th1 and Th2 cytokines (IFN-gamma, TNF-alpha and IL-13). Intestinal permeability was increased and the luminal bacterial flora were more heavily coated with immunoglobulin as occurs in IBD. This pathology was accompanied by accumulation of the Muc2 precursor and ultrastructural and biochemical evidence of endoplasmic reticulum (ER) stress in goblet cells, activation of the unfolded protein response, and altered intestinal expression of genes involved in ER stress, inflammation, apoptosis and wound repair. Expression of mutated Muc2 oligomerization domains in vitro demonstrated that aberrant Muc2 oligomerization underlies the ER stress. These models show that mutations in Muc2 oligomerization domains can lead to aberrant assembly of the Muc2 complex leading to ER stress, a depleted mucus barrier and intestinal inflammation. In ulcerative colitis we demonstrate similar accumulation of non-glycosylated MUC2 precursor in goblet cells together with ultrastructural and biochemical evidence of ER stress even in non-inflamed intestinal tissue. Conclusions; The observations that mucin misfolding and ER stress lead directly to intestinal inflammation and that ER stress and goblet cell pathology occur in ulcerative colitis suggest that ER stress-related mucin depletion could be a fundamental component of the pathogenesis of colitis. Experiment Overall Design: 3 individual mice from the Eeyore, Winnie or Wild-type strains were compared as groups. An Affymetrix ID was compared between groups if the ID was Present within two of the three mice within each grouping. IDs were compared by calculating the log2 of Group One average signal divided by Group 2 average signal.
2008-04-06 | E-GEOD-9913 | biostudies-arrayexpress
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.
2024-01-22 | GSE244377 | GEO
Project description:Background MUC2 mucin produced by intestinal goblet cells is the major component of the intestinal mucus barrier. MUC2 homo-oligomerizes intracellularly into large secreted polymers which give mucus its viscous properties. The inflammatory bowel disease (IBD) ulcerative colitis is characterized by depleted goblet cells and a reduced mucus layer, whereas goblet cells and the mucus layer are increased in the other major inflammatory bowel disease, Crohn’s disease. Methods and Findings By murine N-ethyl-N-nitrosourea-mutagenesis we identified two distinct non-complementing missense mutations in Muc2 exons encoding N- and C-terminal homo-oligomerization domains causing an ulcerative colitis-like phenotype. Both strains developed mild spontaneous distal intestinal inflammation, chronic diarrhea, rectal bleeding and prolapse, increased susceptibility to acute and chronic colitis induced by a luminal toxin, aberrant Muc2 biosynthesis, smaller goblet cell thecae (less stored mucin) and a diminished mucus barrier. Enhanced local production of IL-1beta, TNF-alpha and IFN-gamma was seen in the distal colon. The number of leukocytes within mesenteric lymph nodes was increased five-fold and leukocytes cultured in vitro produced both Th1 and Th2 cytokines (IFN-gamma, TNF-alpha and IL-13). Intestinal permeability was increased and the luminal bacterial flora were more heavily coated with immunoglobulin as occurs in IBD. This pathology was accompanied by accumulation of the Muc2 precursor and ultrastructural and biochemical evidence of endoplasmic reticulum (ER) stress in goblet cells, activation of the unfolded protein response, and altered intestinal expression of genes involved in ER stress, inflammation, apoptosis and wound repair. Expression of mutated Muc2 oligomerization domains in vitro demonstrated that aberrant Muc2 oligomerization underlies the ER stress. These models show that mutations in Muc2 oligomerization domains can lead to aberrant assembly of the Muc2 complex leading to ER stress, a depleted mucus barrier and intestinal inflammation. In ulcerative colitis we demonstrate similar accumulation of non-glycosylated MUC2 precursor in goblet cells together with ultrastructural and biochemical evidence of ER stress even in non-inflamed intestinal tissue. Conclusions The observations that mucin misfolding and ER stress lead directly to intestinal inflammation and that ER stress and goblet cell pathology occur in ulcerative colitis suggest that ER stress-related mucin depletion could be a fundamental component of the pathogenesis of colitis. Keywords: Single gene, multiple mutant comparison
2008-03-01 | GSE9913 | GEO
Project description:Downregulation or gene mutation of MUC6, a major component of gastric mucin, is often identified in human gastric cancers. However, the mechanistic role of MUC6 alteration in gastric carcinogenesis remains unclear. Here, using Muc6-deficient mice, we revealed that dysregulated glycosylation in Muc6-deficient gastric epithelium causes aberrant golgi stress responses, resulting in spontaneous gastric cancer development. Muc6-deficient tumor growth is dependent on MAPK activation, which is mediated by golgi stress-induced golph3 upregulation. Glycomic analysis and lectin-binding assays revealed abnormal expression of mannose-rich N-type glycans in Muc6-deficient gastric tumors. Banana lectin-drug conjugates, which bind to mannose-rich glycans, dramatically suppress mannose-rich murine and human gastric cancer growth. Thus, we propose golgi stress responses and aberrant sugar chains as promising therapeutic targets in gastric cancers accompanied with mucin expression disorder.
2024-08-31 | GSE237686 | GEO
Project description:Downregulation or gene mutation of MUC6, a major component of gastric mucin, is often identified in human gastric cancers. However, the mechanistic role of MUC6 alteration in gastric carcinogenesis remains unclear. Here, using Muc6-deficient mice, we revealed that dysregulated glycosylation in Muc6-deficient gastric epithelium causes aberrant golgi stress responses, resulting in spontaneous gastric cancer development. Muc6-deficient tumor growth is dependent on MAPK activation, which is mediated by golgi stress-induced golph3 upregulation. Glycomic analysis and lectin-binding assays revealed abnormal expression of mannose-rich N-type glycans in Muc6-deficient gastric tumors. Banana lectin-drug conjugates, which bind to mannose-rich glycans, dramatically suppress mannose-rich murine and human gastric cancer growth. Thus, we propose golgi stress responses and aberrant sugar chains as promising therapeutic targets in gastric cancers accompanied with mucin expression disorder.
2024-08-31 | GSE237822 | GEO
Project description:Downregulation or gene mutation of MUC6, a major component of gastric mucin, is often identified in human gastric cancers. However, the mechanistic role of MUC6 alteration in gastric carcinogenesis remains unclear. Here, using Muc6-deficient mice, we revealed that dysregulated glycosylation in Muc6-deficient gastric epithelium causes aberrant golgi stress responses, resulting in spontaneous gastric cancer development. Muc6-deficient tumor growth is dependent on MAPK activation, which is mediated by golgi stress-induced golph3 upregulation. Glycomic analysis and lectin-binding assays revealed abnormal expression of mannose-rich N-type glycans in Muc6-deficient gastric tumors. Banana lectin-drug conjugates, which bind to mannose-rich glycans, dramatically suppress mannose-rich murine and human gastric cancer growth. Thus, we propose golgi stress responses and aberrant sugar chains as promising therapeutic targets in gastric cancers accompanied with mucin expression disorder.
2024-08-31 | GSE237689 | GEO
Project description:PAC polymers of different degrees of polymerization (DP) were used to stimulate murine RAW macrophages.
2021-02-19 | GSE167063 | GEO
Project description:Atherosclerosis is an important pathological factor in the development of cardiovascular diseases. In addition to increased plasma lipid concentrations, irregular/oscillatory shear stress and inflammatory processes trigger pathophysiological changes. Inhibitors of the transcription modulatory bromo- and extra-terminal domain (BET) protein family (BETi) could offer a possible therapeutic approach due to their anti-inflammatory properties. In this study, the influence of laminar shear stress, inflammation and BETi on human endothelial cells in an atherosclerosis in vitro model was investigated using global protein expression profiling. For this purpose, human umbilical cord derived vascular endothelial cells (HUVEC) were treated with TNFα to mimic the inflammatory condition and were exposed to 24h laminar shear stress in the presence or absence of a BRD4 inhibitor, JQ1. Data-independent acquisition mass spectrometry (DIA-MS) alloqed us to quantify 3316 proteins for further statistical analysis. Differentially regulated proteins indicate a clear influence of inflammation and shear stress on human endothelial cells. Overall, application of JQ1 is led to significant changes in the proteome, including a strong anti-inflammatory response as well as a potentially negative impact on atherosclerosis formation. To our knowledge, this is the first proteomics study on HUVEC which investigates the influence of shear stress and BET inhibition in TNFα inflammatory endothelial cell culture model.
2022-10-30 | PXD035842 | Pride