P38a-dependent gene expression in the colonic mucosa
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE55356 | GEO | 2014/07/01
SECONDARY ACCESSION(S): PRJNA239404
REPOSITORIES: GEO
Similar Datasets
Project description:Gene expression in the colonic mucosa of wild-type and p38a-knockout intestinal epithelial cells (IECs) were compared. C57BL/6 wild-type mice, and intestinal epithelial cell-specific p38a-knockout mice on a C57BL/6 background were used for isolation of colonic mucosa Gene expression in each genotype was analyzed in triplicate.
2014-07-01 | E-GEOD-55356 | biostudies-arrayexpress
Project description:The aim of this study is to compare the transcriptomic profile of colonic intestinal epithelial cells (IECs) at steady-state, and in several models of colitis: in naive wild-type C57BL/6 mice, in wild-type C57BL/6 mice treated for 7 days with 3% dextran sodium sulfate (DSS) in drinking water, in Il10-/- C57BL/6 mice and Il10-/- C57BL/6 mice with IEC-specific Rabgef1 deletion. Colonic IECs were isolated and FACS-sorted, then subjected tu bulk RNA-seq.
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Project description:Gene expression in wild-type and p38a-knockout keratinocytes were compared. Keratinocytes were isolated from newborn mice, and left unirradiated (0 h) and irradiated (4 h) with ultraviolet-B (UVB). C57BL/6 wild-type mice, and keratinocyte-specific p38a-knockout mice on a C57BL/6 background were used for isolation of primary keratinocytes.
2014-01-01 | GSE51206 | GEO
Project description:The goal of the present study was to determine whether loss of the insulin receptor alters the molecular landscape of the intestinal mucosa, using intestinal-epithelial insulin receptor knockout (IE-irKO) mice and both genetic (IRfl/fl and Villin-cre) controls. Quantitative proteomic analysis by Liquid Chromatography Mass Spectrometry (LC-MS) was deployed on jejunal and colonic mucosa from mice fed a chow- or Western diet (WD). Jejunal mucosa from IE-irKO mice demonstrated alterations in all intestinal cell linages, Paneth, goblet, absorptive and enteroendocrine cells, whereas only goblet and absorptive cells were affected in the colon. There was also a significant effect of the WD on the gut proteome. A significant reduction was detected in Paneth cell proteins with anti-microbial activity, including lysozyme C-1, angiogenin-4, cryptdin-related sequence1C-3 and -2, a-defensin 17 and intelectin-1a. The key protein expressed by goblet cells, mucin-2, was also reduced in the IE-irKO mice. Proteins involved in lipid metabolism, including aldose reductase-related protein 1, 15-hydroxyprostaglandin dehydrogenase [NAD(+)], apolipoprotein A-II and pyruvate dehydrogenase kinase isozyme 4, were increased in the mucosa of WD-fed IE-irKO mice as compared to controls. In contrast, expression of the nutrient-responsive gut hormones, glucose-dependent insulinotropic polypeptide and neurotensin, was reduced in the jejunal mucosa of IE-irKO mice, and there was a reduction in proteins of the P-type ATPases and the solute carrier-transporter family in the colon of WD-fed IE-irKO mice. In conclusion, IE-irKO mice display a distinct molecular phenotype, suggesting a biological role of insulin and its receptor in determining differentiated cell-specificity in the intestinal epithelium.
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Project description:Gene expression in wild-type and p38a-knockout dendritic cells (DCs) were compared. Lymph node dendritic cells were isolated from mice, and left unstimulated and stimulated with Pam3CSK4, a toll-like receptor 2 agonist. C57BL/6 wild-type mice, and dendritic cell-specific p38a-knockout mice on a C57BL/6 background were used for isolation of primary DCs.
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Project description:We profiled transcriptome and accessible chromatin landscapes in intestinal epithelial cells (IECs) from mice reared in the presence or absence of microbiota. We show that regional differences in gene transcription along the intestinal tract were accompanied by major alterations in chromatin organization. Surprisingly, we discovered that microbiota modify host gene transcription in IECs without significantly impacting the accessible chromatin landscape. Instead, microbiota regulation of host gene transcription might be achieved by differential expression of specific TFs and enrichment of their binding sites in nucleosome depleted CRRs near target genes. Our results suggest that the chromatin landscape in IECs is pre-programmed by the host in a region-specific manner to permit responses to microbiota through binding of open CRRs by specific TFs. mRNA and accessible chromatin (DNase-seq) profiles from colonic and ileal IECs were compared between conventionally-raised (CR), germ-free (GF), and conventionalized (CV) C57BL/6 mice.
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Project description:The microenvironment of injured mucosa has important effects on intestinal stem cell self-renewal and reconstruction of epithelial barrier function in inflammatory bowel disease (IBD). However, the precise status of the interactions between intestinal epithelial cell (IEC) injury, particularly intestinal crypt absence, and microenvironment in IBD is not completely understood. We identified miR-494-3p as important for protection of colonic stemness in intestinal inflammation colonic organoid culture. A novel cytokine-cytokine receptor, EDA-A2/EDA2R, could suppress colonic stemness and epithelial repair during IBD. During intestinal inflammation, high level of LP macrophage-derived EDA-A2 inhibited the nuclear β-catenin/c-Myc axis and organoid growth by targeting EDA2R in colonic crypt stem cells. We further demonstrated that the pro-inflammatory cytokines IL-1β and IL-6 are capable of stimulating macrophages to release EDA-A2 during colitis. Secondly, we identified the cross-talk among IECs, colonic crypts, and lamina propria (LP) macrophages in miR-494-3p-mediated colitis. Furthermore, our study showed that miR-494-3p deficiency in IECs promoted LP macrophage recruitment and M1 activation in DSS-induced colitis mice. In addition, we identified miR-494-3p as critical to dampening IEC injury; specifically, miR-494-3p inhibited inflammation-induced IKKβ/NF-κB activation by targeting the IKKβ 3’UTR in IECs. As such, administration of adequate amounts of a miR-494-3p agomire attenuate colitis in vivo. Consistent with this inference, we showed that miR-494-3p levels were decreased in colonic crypts and serum in colitis mice, and loss of miR-494 potentiated the severity of colonic colitis. Our clinical data on the interactions between miR-494-3p levels in serum exosomes & colonic tissues and associated outcomes support the clinical relevance of miR-494-3p in IBD. The miR-494-3p agomir system, which we designed permits local delivery in vivo in this study, significantly ameliorated the severity of colonic colitis. Our findings no only uncover a miR-494-3p-mediated cross-talk mechanism by which inflamed colonic LP macrophages integrate signals from IECs to regulate colonic stemness and colonic epithelial repair/homeostasis. The miR-494-3p agomir may serve as a potential therapeutic approach in IBD.
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Project description:The microenvironment of injured mucosa has important effects on intestinal stem cell self-renewal and reconstruction of epithelial barrier function in inflammatory bowel disease (IBD). However, the precise status of the interactions between intestinal epithelial cell (IEC) injury, particularly intestinal crypt absence, and microenvironment in IBD is not completely understood. We identified miR-494-3p as important for protection of colonic stemness in intestinal inflammation colonic organoid culture. A novel cytokine-cytokine receptor, EDA-A2/EDA2R, could suppress colonic stemness and epithelial repair during IBD. During intestinal inflammation, high level of LP macrophage-derived EDA-A2 inhibited the nuclear β-catenin/c-Myc axis and organoid growth by targeting EDA2R in colonic crypt stem cells. We further demonstrated that the pro-inflammatory cytokines IL-1β and IL-6 are capable of stimulating macrophages to release EDA-A2 during colitis. Secondly, we identified the cross-talk among IECs, colonic crypts, and lamina propria (LP) macrophages in miR-494-3p-mediated colitis. Furthermore, our study showed that miR-494-3p deficiency in IECs promoted LP macrophage recruitment and M1 activation in DSS-induced colitis mice. In addition, we identified miR-494-3p as critical to dampening IEC injury; specifically, miR-494-3p inhibited inflammation-induced IKKβ/NF-κB activation by targeting the IKKβ 3’UTR in IECs. As such, administration of adequate amounts of a miR-494-3p agomire attenuate colitis in vivo. Consistent with this inference, we showed that miR-494-3p levels were decreased in colonic crypts and serum in colitis mice, and loss of miR-494 potentiated the severity of colonic colitis. Our clinical data on the interactions between miR-494-3p levels in serum exosomes & colonic tissues and associated outcomes support the clinical relevance of miR-494-3p in IBD. The miR-494-3p agomir system, which we designed permits local delivery in vivo in this study, significantly ameliorated the severity of colonic colitis. Our findings no only uncover a miR-494-3p-mediated cross-talk mechanism by which inflamed colonic LP macrophages integrate signals from IECs to regulate colonic stemness and colonic epithelial repair/homeostasis. The miR-494-3p agomir may serve as a potential therapeutic approach in IBD.
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Project description:Citrobacter rodentium is commonly used to elucidate mucosal responses to infection in mice developing mild disease (e.g. C57BL/6), while little is known about host responses to infection in mice developing severe disease (e.g. C3H/HeN). We report that the phyla Bacteroidetes is a minor component of the tissue-associated microbiome in uninfected C3H/HeN mice. Following infection, C. rodentium rapidly and uniformly colonises the C3H/HeN colonic mucosa, which coincides with downregulation of proteins involved in the TCA cycle and oxidative phosphorylation in intestinal epithelial cells (IECs). In contrast, we observed upregulation of DNA replication and DNA damage repair processes, as well as cholesterol biogenesis, import and export, nutritional immunity, IL-22 and INFg responses, and expression of NLRP3, in IECs. Moreover, C. rodentium triggers a staggered cell proliferation response from 3 days post infection, which correlated with a higher abundance of SLC5A9 and reduced abundance of the IEC differentiation markers SLC26A3 and CA4. Uniquely, C. rodentium triggers differential secretion of gel-forming mucins, with the number of goblet cells filled with acidic and neutral mucins dramatically increasing and decreasing, respectively. Together, these results show that despite vigorous responses, C3H/HeN mice succumb to C. rodentium infection, possibly as a result of excessive and disordered mucosal responses.
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