XBP1 is the transcriptino factor that is activated by the ER stress. XBP1 is known to induce the ER dexpansion and increase the expression of the ER chaperone genes to prtect the cell from the ER stress. We generated a mouse strain that lacked XBP1 specifically in the mouse intestine by breeding the XBP1flox mice with Villin-cre mice. Here we examined genes that are differentially expressed between WT and XBP1 KO mouse intestine to identify genes that are downstream of XBP1.
XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease.
No sample metadata fields
View SamplesMolecular adaptation of the intestinal mucosa occurs during microbial conventionalization to maintain a balanced immune response. However, the genetic regulation of such adaptation is obscure. Here, combined analysis of germ free and conventionalized mice revealed that the major molecular adaptations were initiated at day 4 of conventionalization with a strong induction of innate immune functions followed by stimulation of adaptive immune functions. We identified central regulatory genes and reconstructed a common regulatory network that appeared to be sufficient to regulate the dynamic adaptation of the intestinal mucosa to the colonizing microbiota. The majority of the genes within this regulatory network play roles in mucosal inflammatory diseases in mouse and human. We propose that the identified central regulatory network may serve as a genetic signature for control of intestinal homeostasis in healthy mice and may help to unravel the genetic basis of pathway dysregulation in human intestinal inflammatory diseases.
Temporal and spatial interplay of microbiota and intestinal mucosa drive establishment of immune homeostasis in conventionalized mice.
Sex, Specimen part
View SamplesBmdm cells were differentiated for 10 days and harvested and culture in six well plate followed by cytokine stimulation after 24 hrs cells were infected with mycobacterium tuberculosis to identify the host factors involved in infection.
IL-4Rα-dependent alternative activation of macrophages is not decisive for Mycobacterium tuberculosis pathology and bacterial burden in mice.
Sex, Specimen part
View SamplesClinical remission is apparent when laboratory markers of inflammation are normal and clinical symptoms are absent. However, sub-clinical inflammation can still be present. A detailed analysis of the immune status during this inactive state of disease may provide a useful tool to subcategorize patients with subclinical immune activation
Gene expression analysis of peripheral cells for subclassification of pediatric inflammatory bowel disease in remission.
Specimen part
View SamplesLipid overload and adipocyte dysfunction are key to the development of insulin resistance and can be induced by a high-fat diet. CD1d-restricted invariant natural killer T (iNKT) cells have been proposed as mediators between lipid overload and insulin resistance, but recent studies found decreased iNKT cell numbers and marginal effects of iNKT cell depletion on insulin resistance under high-fat diet conditions. Here, we focused on the role of iNKT cells under normal conditions. We showed that iNKT celldeficient mice on a low-fat diet, considered a normal diet for mice, displayed a distinctive insulin resistance phenotype without overt adipose tissue inflammation. Insulin resistance was characterized by adipocyte dysfunction, including adipocyte hypertrophy, increased leptin, and decreased adiponectin levels. The lack of liver abnormalities in CD1d-null mice together with the enrichment of CD1d-restricted iNKT cells in both mouse and human adipose tissue indicated a specific role for adipose tissueresident iNKT cells in the development of insulin resistance. Strikingly, iNKT cell function was directly modulated by adipocytes, which acted as lipid antigen-presenting cells in a CD1d-mediated fashion. Based on these findings, we propose that, especially under low-fat diet conditions, adipose tissueresident iNKT cells maintain healthy adipose tissue through direct interplay with adipocytes and prevent insulin resistance.
Natural killer T cells in adipose tissue prevent insulin resistance.
Specimen part
View SamplesPersistent severe asthma is associated with hyper-contractile airways and structural changes in the airway wall, including an increased airway smooth muscle (ASM) mass. This study used gene expression profiles from asthmatic and healthy airway smooth muscle cells grown in culture to identify novel receptors and pathways that potentially contributed to asthma pathogenesis.
Latrophilin receptors: novel bronchodilator targets in asthma.
Sex, Disease, Treatment
View SamplesBackground and aim: The Insulin-like growth factor (IGF) axis is increasingly suggested to be involved in fatty liver disease and progression. We identified IGFBP2 as transcriptional regulatory effect network in liver steatosis and conducted a translational approach of its role in liver pathology from mouse to human, and whether it is influenced by conventional clinical intervention that mitigate hepatic steatosis. Methods: Primary hepatocytes from either C57Bl6 controls, alb-SREBP-1c mice with moderate transgene induced hepatic lipid accumulation or aP2-SREBP-1c mice with massive ectopic hepatic lipid accumulation, were analyzed to identify regulatory networks based on differentially regulated hepatic gene expression. In a translational approach, serum of morbidly obese patients with and without diabetes and biopsy-proven NAFLD were used for ELISA-based validation of mouse data. Moreover, sera of patients undergoing intervention were analyzed and correlated to liver fat content. Results: Comparative knowledge-based transcriptome analysis identified IGFBP2 as top score regulatory effect network between moderate and aggravated fatty liver in mouse models. The reduced expression of IGFBP2 in aP2-SREPB-1c progressed fatty liver associated with Igfbp2 promoter hypermethylation. Reduced secretion of IGFBP2 from aP2-SREBP-1c hepatocytes was reflected in the circulation of the animals. In this phenotype, reductions of IGFBP2 were accompanied by reduced fatty acid oxidation and increased methyltransferase and SIRT activity. Physiologically, IGFBP2 has no direct impact on lipid metabolism but might modulate IGF1 action on de novo lipogenesis. In humans, IGFBP2 levels declined from non-obese men to morbidly obese men with NAFLD and NASH. In intervention study reductions in liver fat correlated with restoration of IGFBP2 serum levels to values found in healthy individuals in morbidly obese patients following bariatric surgery. Conclusion: In hepatic metabolism changes of IGFBP2 abundance is connected to lipid metabolism whereas changes in IGFBP2 secretion were directly reflected in the circulation. IGFBP2 serum concentration correlates with the degree of fatty liver, which seems to be related to plasticity of the adipose tissue. These data provide IGFBP2 as a potential non-invasive biomarker for fatty liver disease directly reflecting the degree of impaired liver function with the potential to indicate progressed fatty liver disease.
Physiological Disturbance in Fatty Liver Energy Metabolism Converges on IGFBP2 Abundance and Regulation in Mice and Men.
Sex, Age
View SamplesAdam10, a cell surface protease, cleaving many proteins including TNF-alpha and E-cadherin. Here we investigate the genome wide effects of Adam10 knock out on the transcriptome.
The disintegrin/metalloproteinase Adam10 is essential for epidermal integrity and Notch-mediated signaling.
Specimen part
View SamplesThe endoplasmic reticulum (ER) is the site of secretory lipoprotein production and de novo cholesterol synthesis, yet little is known about how these activities are coordinated with each other, or with the activity of the COPII machinery, which transports ER cargo to the Golgi. The Sar1B component of this machinery is mutated in Chylomicron Retention Disorder, establishing that this Sar1 isoform secures delivery of dietary lipids into the circulation.
The endoplasmic reticulum coat protein II transport machinery coordinates cellular lipid secretion and cholesterol biosynthesis.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Drug-induced histone eviction from open chromatin contributes to the chemotherapeutic effects of doxorubicin.
Age, Specimen part, Cell line, Treatment, Time
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