Background & Aims: The role of HNF4 has been extensively studied in hepatocytes and pancreatic cells, but emerging evidence indicates that HNF4 is a key regulator of intestinal epithelial cell differentiation as well. The aim of the present work is to identify HNF4 target genes in the intestine in order to elucidate the role of HNF4 in differentiation of the intestinal epithelial cells. Results: One thousand one hundred and seventy-six genes were identified as HNF4 targets, many of which have not previously been described as being regulated by HNF4. The 1,176 genes contributed significantly to gene ontology (GO) pathways categorized by lipid and amino acid transport and metabolism. A thorough analysis of Cdx-2, trehalase, and cingulin promoters verified that these genes are regulated by HNF4. In each case we were able to identify a functional HNF4 binding site in their promoters. Conclusions: HNF4 regulation of the Cdx-2 promoter unravels a transcription factor network also including HNF1 and , all of which are transcription factors involved in intestinal development and gene expression.
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View SamplesThe epithelial expression of the insulin receptor in the colon is previously reported to correlate with the extent of colonic inflammation. Here, we investigated the effect of inactivating the epithelial insulin receptor in the intestinal tract, in an experimental model of inflammation-induced colorectal cancer. We report increased susceptibility to chemically-induced colitis together with potentiated colonic tumorigenesis in the knockout mice. Furthermore, we show that topically administered insulin in inflamed colons of wildtype mice reduces inflammation-induced weight loss and improves remission in a dose-dependent manner. Mice receiving rectal insulin enemas exhibited lower colitis endoscopic scores and developed significantly fewer and smaller tumors compared with the control group receiving phosphate-buffered saline only. Rectal insulin therapy can potentially be a novel treatment targeting the epithelial layer to enhance mucosal healing in the ulcerated areas. Our findings open up new possibilities for combination treatments to synergize with the existing anti-inflammatory therapies.
Rectal Insulin Instillation Inhibits Inflammation and Tumor Development in Chemically Induced Colitis.
Treatment
View SamplesGene expression of P. aerruginosa changes after short-term exposure to ciprofloxacin at sub-inhibitory concentrations but the effect of long-term exposure which select for the most fitted subpopulations is not known.
The phenotypic evolution of Pseudomonas aeruginosa populations changes in the presence of subinhibitory concentrations of ciprofloxacin.
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View SamplesGenes involved in the inflammatory response resulting in allergic contact dermatitis (ACD) are only partly known. In this study, we introduce the use of high density oligonucleotide arrays for gene expression profiling in human skin during the elicitation of ACD. Skin biopsies from normal and nickel-exposed skin were obtained from 7 nickel-allergic patients and 5 non-allergic controls at four different time points during elicitation of eczema: 0h, 7h, 48h and 96h. Each gene expression profile was analysed by hybridization to high density oligonucletide arrays.
Gene expression time course in the human skin during elicitation of allergic contact dermatitis.
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View SamplesPurpose: The complement system is closely linked to the pathogenesis of age-related macular degeneration (AMD). Several complement genes are expressed in retinal pigment epithelium (RPE), and complement proteins accumulate in drusen. Further, a common variant of complement factor H (CFH) confers increased risk of developing AMD. Because the mechanisms by which changes in the function of CFH influence development of AMD are unclear, we examined ocular complement expression as a consequence of age in control and CFH null mutant mice.
Complement factor H deficiency results in decreased neuroretinal expression of Cd59a in aged mice.
Specimen part
View SamplesPurpose
Chemokine Expression in Murine RPE/Choroid in Response to Systemic Viral Infection and Elevated Levels of Circulating Interferon-γ.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity.
Specimen part
View SamplesAtopic dermatitis (AD) is a common inflammatory skin disease with underlying defects in epidermal function and immune responses. The goal of this study was to investigate differences in gene expression in lesional skin from patients with mild extrinsic or intrinsic AD compared to skin from healthy controls and from lesional psoriasis skin. The aim was to identify differentially expressed genes involved in skin barrier formation and inflammation, and to compare our results with those reported for patients with moderate and severe AD.
Distinct molecular signatures of mild extrinsic and intrinsic atopic dermatitis.
Specimen part, Disease
View SamplesCytoglobin is a member of the hemoglobin family and is thought to protect against cellular hypoxia and cellular oxidative stress. This function may be particularly important in inflammation induced cancer observed in e.g. patients with ulcerative colitis. In this study, we investigated the development of inflammation and tumors in the murine model of inflammation induced colorectal cancer using Azoxymethane treatment combined with Dextrane Sodium Sulphate.
No associated publication
Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Weight loss after gastric bypass surgery in human obesity remodels promoter methylation.
Sex, Specimen part
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