Similar Datasets
Project description:To investigate the role of claudin-2 in IBD and collitis-associated colon cancer
2025-06-27 | GSE207220 | GEO
Project description:Claudin2 Upregulation: IBD and colitis-associated colon cancer
| PRJNA854172 | ENA
Project description:Claudin2 Upregulation: IBD and colitis-associated cancer [knockout]
| PRJNA854177 | ENA
Project description:The mucosal epithelium plays a key role in regulating immune homeostasis. Dysregulation of epithelial barrier function is associated with mucosal inflammation. Expression of claudin-2, a pore-forming tight junction protein, is highly upregulated during inflammatory bowel disease (IBD) and, due to its association with epithelial permeability, has been postulated to promote inflammation. Furthermore, claudin-2 also regulates colonic epithelial cell proliferation and intestinal nutrient absorption. However, the precise role of claudin-2 in regulating colonic epithelial and immune homeostasis remains unclear. Here, we demonstrate, using Villin-Claudin-2 transgenic (Cl-2TG) mice, that increased colonic claudin-2 expression unexpectedly protects mice against experimentally induced colitis and colitis-associated cancer. Notably, Cl-2TG mice exhibited increased colon length and permeability as compared with wild type (WT) littermates. However, despite their leaky colon, Cl-2TG mice subjected to experimental colitis were immune compromised, with reduced induction of TLR-2, TLR-4, Myd-88 expression and NF-kB and STAT3 activation. Most importantly, colonic macrophages in Cl-2TG mice exhibited an anergic phenotype. Claudin-2 overexpression also increased colonocyte proliferation and provided protection against colitis-induced colonocyte death. Taken together, our findings have revealed a critical role of claudin-2 in regulating colonic homeostasis, suggesting novel therapeutic strategies for inflammatory conditions of the gastrointestinal tract. 8-10 weeks old male Villin-Claudin-2 transgenic mice and WT littermates were provided either normal drinking water (control) or Dextran Sodium Sulfate (DSS: 4% w/v) for 10 days. 3 replicates each.
2013-09-15 | E-GEOD-46006 | biostudies-arrayexpress
Project description:The mucosal epithelium plays a key role in regulating immune homeostasis. Dysregulation of epithelial barrier function is associated with mucosal inflammation. Expression of claudin-2, a pore-forming tight junction protein, is highly upregulated during inflammatory bowel disease (IBD) and, due to its association with epithelial permeability, has been postulated to promote inflammation. Furthermore, claudin-2 also regulates colonic epithelial cell proliferation and intestinal nutrient absorption. However, the precise role of claudin-2 in regulating colonic epithelial and immune homeostasis remains unclear. Here, we demonstrate, using Villin-Claudin-2 transgenic (Cl-2TG) mice, that increased colonic claudin-2 expression unexpectedly protects mice against experimentally induced colitis and colitis-associated cancer. Notably, Cl-2TG mice exhibited increased colon length and permeability as compared with wild type (WT) littermates. However, despite their leaky colon, Cl-2TG mice subjected to experimental colitis were immune compromised, with reduced induction of TLR-2, TLR-4, Myd-88 expression and NF-kB and STAT3 activation. Most importantly, colonic macrophages in Cl-2TG mice exhibited an anergic phenotype. Claudin-2 overexpression also increased colonocyte proliferation and provided protection against colitis-induced colonocyte death. Taken together, our findings have revealed a critical role of claudin-2 in regulating colonic homeostasis, suggesting novel therapeutic strategies for inflammatory conditions of the gastrointestinal tract.
2013-09-15 | GSE46006 | GEO
Project description:To clarify the pathological significance of CGRP in ulcerative colitis, we generated knockout mice for CGRPα and CGRPβ and analyzed colon proteome data from DDS drinking water ulcerative colitis model mice. In addition, to confirm changes in the colon over time, the colon of wild-type mice after DDS drinking was harvested over time and used for proteome data.
2024-09-23 | PXD055368 | JPOST Repository
Project description:The transcriptional signature of mucosa of patients with ulcerative colitis (UC) in remission reveals long-lasting changes in the epithelial barrier which persist once the inflammatory response has resolved. In order to investigate if these changes are caused by primary defects in the epithelial cells, we generated in vitro epithelial organoid cultures (EpOCs) from colon samples of non-IBD controls and UC patients. After induction of differentiation, total RNA was extracted from both EpOCs and differentiated EpOCs (d-EpOCs) and used for hybridization on Affymetrix microarray.
2016-11-02 | GSE75916 | GEO
Project description:MUC1 is a tumor-associated antigen that is aberrantly expressed in cancer and inflammatory bowel disease (IBD). Even though immune cells express low MUC1 levels, their modulations of MUC1 are important in tumor progression. Consistent with previous clinical data that show increased myeloid-derived suppressor cells (MDSCs) in IBD, we now show that down-regulation of MUC1 on hematopoietic cells increases MDSCs in IBD, similar to our data in tumor-bearing mice. We hypothesize that MDSC expansion in IBD is critical for tumor progression. In order to mechanistically confirm the linkage between Muc1 down-regulation and MDSC expansion, we generated chimeric mice that did not express Muc1 in the hematopoietic compartment (KOM-bM-^FM-^RWT). These mice were used in 2 models of colitis and colitis-associated cancer (CAC) and their responses were compared to wildtype chimeras (WTM-bM-^FM-^RWT). KOM-bM-^FM-^RWT mice show increased levels of MDSCs during colitis that was responsible for the larger colon tumors that eventually developed in these mice. Using microarray and qRT-PCR analysis, we observed increased pro-tumorigenic signaling in the colons of KOM-bM-^FM-^RWT mice during colitis as compared to WTM-bM-^FM-^RWT mice. Our RNA (microarray and qRT-PCR analysis) and protein analysis demonstrate increased up-regulation of metalloproteinases, collagenases, defensins, complements, growth factors, cytokines and chemokines in KOM-bM-^FM-^RWT mice as compared to WTM-bM-^FM-^RWT mice. Antibody-mediated depletion of MDSCs in mice during colitis reduced colon tumor formation during CAC. Development of CAC is a serious complication of colitis and our data highlight MDSCs as a targetable link between inflammation and cancer. A total of 12 samples were analysed. RNA was made from the mucosa of the colon of WTM-bM-^FM-^RWT and KOM-bM-^FM-^RWT mice that were either untreated or treated with azoxymethane (AOM) and dextran sodium sulfate (DSS). There are 4 groups, n=3 for each group: untreated WTM-bM-^FM-^RWT mice, untreated KOM-bM-^FM-^RWT mice, AOM+DSS treated WTM-bM-^FM-^RWT mice, AOM+DSS treated KOM-bM-^FM-^RWT mice = 12 samples in total.
2013-05-30 | E-GEOD-47487 | biostudies-arrayexpress
Project description:Pediatric-onset colitis and inflammatory bowel disease (IBD) have significant effects on the growth of infants and children, but the etiopathogenesis underlying disease subtypes remains incompletely understood. Here, we report single-cell clustering, immune phenotyping, and risk gene analysis for children with undifferentiated colitis, Crohn’s disease, and ulcerative colitis. We demonstrate disease-specific characteristics, as well as common pathogenesis marked by impaired cyclic AMP (cAMP)-response signaling. Specifically, infiltration of PDE4B- and TNF-expressing macrophages, decreased abundance of CD39-expressing intraepithelial T cells, and platelet aggregation and release of 5-hydroxytryptamine at the colonic mucosae were common in colitis and IBD patients. Targeting these pathways by using the phosphodiesterase inhibitor dipyridamole restored immune homeostasis and improved colitis symptoms in a pilot study. In summary, comprehensive analysis of the colonic mucosae has uncovered common pathogenesis and therapeutic targets for children with colitis and IBD.
2019-11-22 | GSE121380 | GEO
Project description:'Illumina Infinium HumanMethylation450 BeadChip data from CD326+ sorted colonic epithelial cells of mucosal biopsies from treatment-naive paediatric IBD patients (Crohn''s Disease or Ulcerative Colitis) or age-matched controls AC= ascending colon, PSC=sigmoid colon'
2015-09-15 | E-MTAB-3709 | biostudies-arrayexpress