Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA205858 | ENA |
REPOSITORIES: ENA
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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 (KO→WT). These mice were used in 2 models of colitis and colitis-associated cancer (CAC) and their responses were compared to wildtype chimeras (WT→WT). KO→WT 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 KO→WT mice during colitis as compared to WT→WT 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 KO→WT mice as compared to WT→WT 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.
2013-05-30 | GSE47487 | 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:Colitis is associated with the development of colorectal cancer (CRC) by largely undefined mechanisms that are critical for understanding the link between inflammation and cancer. Intestinal stem cells (ISCs) marked by LGR5 expression are of importance in both the inflammatory response to colitis and progression to colitis-associated colon cancer (CACC). Here, we report in human MUC1-transgenic mouse models of CACC that targeting the MUC1-C oncogenic protein, which is upregulated in inflammation, suppresses the (i) Lgr5+ ISC population, (ii) induction of Myc and core pluripotency stem cell factors, and (iii) severity and progression of colitis to dysplasia and cancer. By extension to human colon cancer cells, we demonstrate that MUC1-C drives MYC, forms a complex with MYC on the LGR5 promoter and activates LGR5 expression. We also show in CRC cells that MUC1-C induces the cancer stem cell (CSC) markers (BMI1, ALDH1, FOXA1, LIN28B) and the OCT4, SOX2 and NANOG pluripotency factors. Consistent with conferring the CSC state, targeting MUC1-C suppresses the capacity of CRC cells to promote wound healing, invasion, self-renewal and tumorigenicity. In analysis of human tissues, MUC1 expression associates with activation of inflammatory pathways, development of colitis and aggressiveness of CRCs. These results collectively indicate that MUC1-C is of importance for integrating stemness and pluripotency in colitis and CRC. Of clinical relevance, the findings further indicate that MUC1-C represents a previously unrecognized target that is druggable for treating progression of colitis and CRC.
2020-10-12 | GSE144319 | GEO
Project description:Gene expression analysis of sorted colon macrophages of Rictor fl/fl LysM+/+ and Rictor fl/fl LysM+/cre mice Dysregulations of immune and metabolic processes can lead to chronic inflammation, which is one of the driving forces for the development of cancer. Macrophages are regulators of these processes and therefore have a fundamental role for the initiation of cancer. Here we find that deletion of Rictor in myeloid cells increases tumor number and size in the colitis-associated colorectal cancer model and leads to a stronger inflammatory response in the underlying acute DSS-colitis model. OPN is shown to be upregulated in the serum of myeloid-specific Rictor-KO mice during the DSS-colitis and the more severe phenotype, characterized by decreased survival, increased weight loss, shorter colons and enhanced infiltration of immune cells into the colon, can be reverted by the neutralization of OPN in these mice. Microarray analysis reveals a change in inflammatory and metabolic gene signatures of Rictor-KO colon macrophages that is also seen in the Rictor-KO BMDM in vitro. Therefore, our data show that myeloid Rictor controls macrophage polarization and the cellular energy metabolism, thereby suppressing colitis and colitis-associated colorectal cancer.
2019-11-12 | GSE96525 | 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:That commensal bacteria can influence intestinal inflammation has been observed using other models of chronic colitis. Loss of IL-10, a major immunosuppressive cytokine, induces spontaneous colitis in mice. The incidence of spontaneous polyp formation in IL-10-deficient mice was also completely eliminated in the absence of STING We used microarrays to evaluate the inflammatory cytokine expression in the colon from IL10 KO mice and IL10/STING KO mice.
2018-02-01 | GSE107810 | GEO
Project description:To screen mRNAs specifically regulated by mTORC1, a global mRNA expression profile in colon epithelial cells (CECs) from mice with or without CECs-specific TSC1 knockout (KO) was developed using microarray. Wile-type or CECs-specific TSC1 KO mice with experimental colitis were sacrificed, with CECs harvested and subjected to total RNA extraction.
2015-11-05 | E-GEOD-74674 | biostudies-arrayexpress
Project description:In this study, to investigate the role of macrophage GIV in the colon, Katkar et al. employed a myeloid-specific GIV-KO (Ccdc88afl/fl/LysMCre) mouse model to analyze colon transcriptomic data from wild-type (WT) and macrophage-specific GIV-KO mice treated with dextran sulfate sodium (DSS) colitis, with or without muramyl dipeptide (MDP) treatment.
2025-09-18 | GSE299285 | GEO
Project description:Temporal genome profiling of DSS colitis The DSS induced mouse colitis model is often used to emulate Ulcerative Colitis (UC) in order understand pathophysiological mechanism of inflammatory bowel disease (IBD). Given the progressive nature of IBD, colon tissue gene expression changes during the evolution of disease, and knowing the changes in gene expression profiles could indentify potential diagnostic markers or additional therapeutic targets for colitis. Therefore, we performed temporal genome expression profiling analysis using the Affymetrix genome wide microarray system to identify broad scale changes in gene expression associated with the development of colitis. Keywords: Expression time course of mouse colon tissue induced by 3% DSS. C57BL/6J mice were given 3% DSS in the drinking water and tissues from individual cohorts were collected at days 0, 2, 4 and 6. Total RNA were extracted from the colon tissue and detected by Affymerix GeneChip Mouse Genome 430 2.0 Array.
2010-10-13 | E-GEOD-22307 | biostudies-arrayexpress
Project description:The identification of inflammatory bowel disease (IBD) susceptibility genes by genome-wide association has linked this pathology to autophagy, a lysosomal degradation pathway that is crucial for cell and tissue homeostasis. Here, we describe autophagin-1 (ATG4B) as an essential protein in the control of inflammatory response during experimental colitis. In this pathological condition, ATG4B protein levels increase paralleling the induction of autophagy. Moreover, ATG4B expression is significantly reduced in affected areas of the colon from IBD patients. Consistently, atg4b-/- mice present Paneth cell abnormalities, as well as an increased susceptibility to DSS-induced colitis. Atg4b-deficient mice exhibit significant alterations in proinflammatory cytokines and mediators of the immune response to bacterial infections, which are reminiscent of those found in patients with Crohn’s disease or ulcerative colitis. Additionally, antibiotic treatments and bone marrow transplantation from wild-type mice reduced colitis in atg4b-/- mice. Taken together, these results provide additional evidence on the importance of autophagy in intestinal pathologies and describe ATG4B as a novel protective protein in inflammatory colitis. Finally, we propose that Atg4b-null mice are a suitable model for in vivo studies aimed at testing new therapeutic strategies for intestinal diseases associated with autophagy deficiency Seven samples were collected in total: three from wild-type mice (1 from the ileum and the colon of control mice, and 1 from the colon of a DSS-treated mouse) and four from Atg4b knock-out mice (1 from the ileum and the colon of control mice, and 2 from the colon of DSS-treated mice).
2013-09-16 | E-GEOD-36056 | biostudies-arrayexpress