CSE-induced hydorogen sulfide improves glucose homeostasis and inhibits beta-cell failure in high-fat diet mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Toshihide Kimura
PROVIDER: E-GEOD-50458 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:CSE knockout (CSE-KO)mice at age 6 months were fed a high fat diet (HFD) for 8 weeks.we determined the effects of CSE knockdown on beta-cell function and mass in islets from the mice. After 8 weeks of the HFD,blood glucose levels were drasically increaced in CSE-KO mice compared with WT mice. To assess the effect of HFD on gene expression in CSE-KO mice,we performed a comparative DNA microarray analysis
2013-09-02 | GSE50458 | GEO
Project description:To elucidate differential gene expression pattern in atopic diathesis model mice spinal cord microglia compared to normal mice. Sort microglia from atopic diathesis model mice and control mice, extract RNA and subjected to RNA array assay.
2015-07-09 | E-GEOD-68202 | biostudies-arrayexpress
Project description:The circadian clock has been found to be associated with various diseases. We showed that 5/6 nephrectomy (5/6Nx) Clk/Clk mice, which show mutation in the gene encoding circadian locomotor output cycles (Clock) do not show aggravation of renal fibrosis because transforming growth factor-1 (Tgf-1) expression is not increased. In wild-type 5/6Nx kidneys, we found that retinoid, a metabolite of retinol, led to alteration of the expresion 24-h rhythm of Clock expression. Renal Tgf- 1 expression is activated by Clock and further aggravates renal dysfunction by causing fibrosis. We also showed that, in 5/6Nx mice fed a retinol-free diet, renal fibrosis and apoptosis are reduced, leading to a marked improvement in serum creatinine levels. Moreover, our study identified hepatic Cyp3a11 and Cyp26a1 as key retinol metabolism-related genes whose expression decreased in 5/6Nx mice. Our data indicated that the negative chain reaction of metabolic clock alteration in between the kidney and liver aggravates renal dysfunction. Differential gene expression between retinol (-) feeding and clock mutant in 5/6 nephrectomized mouse was measured on the kidney at 8 weeks after operation. Four-week-old male ICR mice (Charles River Japan, Inc., Yokohama, Japan) were housed in a light-controlled room (lights on from Zeitgeber time [ZT] 0 to ZT12) at 24 ± 1°C and 60 ± 10% humidity, with food and water available ad libitum. Mice were synchronized to the lighting conditions for 2 weeks before surgery. Male ICR mice (5 weeks old) were purchased from Charles River Japan, Inc. (Kanagawa, Japan). Clock mutant mice (C57BL/6J-ClockmlJt/J) were purchased from The Jackson Laboratory (Bar Harbor, ME, USA). We placed them in the ICR genetic background to enhance breeding robustness and care of the young. These mice were backcrossed using a Jcl:ICR background for more than eight generations. We prepared mouse models of CRF by 5/6Nx operation (Ope) under sodium pentobarbital (40 mg/kg, i.p.) or diethyl ether anesthesia. 5/6Nx was performed in two stages. In the first surgical procedure (at 6 weeks of age), two-thirds of the left kidney was removed by cutting off both poles. Seven days later, the right kidney was completely removed. After the operation, mice were housed for 8 weeks (until they were 16 weeks old) in order to achieve CRF. Sham-operated (Sham) mice were subjected to laparotomy on the same days as the procedure in the 5/6Nx mice. This method was also used for treating Clk/Clk mice. Retinol-free food (A minus) was purchased form KBT ORIENTAL CO., LTD. To investigate the influences of retinol-free feeding on kidney, mice were fed from the fourth week to the eighth week after an operation.
2014-06-06 | E-GEOD-57799 | biostudies-arrayexpress
Project description:Novel therapies targeting cancer stem cells (CSCs), which play critical roles in chemo- and radio-resistance, metastasis, and possibly resistance against cancer immunotherapy including granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-transduced tumor cell vaccines, may provide beneficial clinical outcomes. Here, we used syngeneic immunocompetent mice that allowed precise evaluation of the immunogenicity of the side population (SP) isolated from 4T1 murine breast carcinoma (4T1-SP) cells as putative CSCs. 4T1-SP cells showed various stem cell properties including high capacities for colony formation and tumorigenicity as well as high expression of phosphorylated signal transducer and activator of transcription-3 and vascular endothelial growth factor that are inductive of immune tolerance. Despite these progressive malignant characteristics of 4T1-SP cells, subcutaneous injection of non-transmissible Sendai virus-mediated GM-CSF gene-transduced 4T1-SP (4T1-SP/GM) cells remarkably impaired their tumorigenicity compared with that of the controls. This impairment of tumorigenicity was partially dependent on CD8+ T cells in concert with CD4+ T cells and natural killer cells. Notably, therapeutic vaccinations using irradiated 4T1-SP/GM cells markedly suppressed tumor development of subcutaneously transplanted 4T1-SP cells compared with that of the controls including irradiated 4T1-non-SP/GM cells. Tumor suppression was accompanied by robust accumulation of mature dendritic cells at vaccination sites and systemic Th1-based cellular immunity. Moreover, vaccinations comprising primary 4T1-SP cells isolated from transplanted 4T1-SP tumors elicited antitumor effects. cDNA microarray analysis showed that 4T1-SP cells predominantly expressed genes of cancer-related antigens including cancer/testis antigens. Collectively, we demonstrate that SP cell-based vaccinations induce effective antitumor immunity that may improve the efficacy of SP cell-based immunotherapy. Gene expression profiles were compared between sorted 4T1-SP and 4T1-NSP cells.
2014-04-01 | E-GEOD-53444 | biostudies-arrayexpress
Project description:Controlling metastatic lesions is an important part of improving cancer prognosis, in addition to controlling the primary lesion. There have been many histological examinations of primary and metastatic lesions, but little basic research using cell strains from primary and metastatic lesions belonging to the same patient. In this study, we successfully established a cell strain derived from lower gingival carcinoma (WK2) and a strain derived from secondary cervical lymph node metastasis (WK3F) through primary cultures of tissue from a patient with oral squamous cell carcinoma. We then investigated the biological characteristics of the cancer cell strains from these primary and metastatic lesions, and analyzed metastasis-related genes. Comparing the biological characteristics in vitro showed WK3F to have higher cell proliferation ability and shorter cell doubling time than WK2. It also showed increased cell migratory ability, and high invasive and self-replication abilities. Heterotransplantation into nude mice resulted in high tumor formation rates in the tongue and high metastasis rates in the cervical lymph nodes. Changes in WK2 and WK3F gene expression were comprehensively analyzed with the microarray method. Genes with increased expression in WK3F compared to WK2 were extracted when Z-score ≥ 2.0 and ratio ≥ 5.0, while genes with reduced expression in WK3F compared to WK2 were extracted when Z-score ≤ -2.0 and ratio ≤ 0.2. As a result, differences were found in 604 genes. From these, MAGEC1 (88.0 times), MMP-7 (18.6 times), SNAI1 (6.6 times), MACC1 (6.2 times), and HTRA1 (0.012 times) were selected as metastasis-related candidate genes. The results suggest that these molecules could be important to clarifying the mechanism of metastasis, and could become therapeutic targets. We successfully established a cell strain derived from lower gingival carcinoma (WK2) and a strain derived from secondary cervical lymph node metastasis (WK3F) through primary cultures of tissue from a patient with oral squamous cell carcinoma. Changes in WK2 and WK3F gene expression were comprehensively analyzed with the microarray method.
2014-06-30 | E-GEOD-54672 | biostudies-arrayexpress
Project description:In addition to their role as a digestive detergent, bile acids have the ability to modulate the expression of genes. The intestinal content of cholic acids (CA) fluctuated in response to the daily feeding-fasting cycle; therefore, we hypothesized that the temporal accumulation of CA may affect the expression of genes in intestinal epithelial cells. To screen bile acid-regulated genes, we performed oligonucleotide microarray analyses using RNA isolated from the CA-treated intestinal cells of mice. Several types of genes were screened as candidates for bile acid-regulated genes. They included genes that encoded lipid metabolism-related proteins, receptors, transcriptional factors, and plasma-membrane transporters. Total 2 samples were derived from [1] vehicle (0.05% DMSO and 0.25% ethanol)-treated intestinal epithelial cells of mice and [2] cholic acid (CA)-treated intestinal epithelial cells of mice.
2015-08-01 | E-GEOD-55443 | biostudies-arrayexpress
Project description:Background: EGFRvIII is a mutant form of the epidermal growth factor receptor gene (EGFR) that lacks exons 2-7. The resulting protein does not bind to ligands and is constitutively activated. The expression of EGFRvIII is likely confined to various types of cancer, particularly glioblastomas. Although an anti-EGFRvIII vaccine is of great interest, low-molecular-weight substances are needed to obtain better therapeutic efficacy. Thus, the purpose of this study is to identify low molecular weight substances that can suppress EGFRvIII-dependent transformation. Methods: We constructed a new throughput screening system and searched for substances that decreased cell survival of NIH3T3/EGFRvIII spheres under 3-dimensional (3D)-culture conditions, but retained normal NIH3T3 cell growth under 2D-culture conditions. In vivo activity was examined using a mouse transplantation model, and derivatives were chemically synthesized. Functional characterization of the candidate molecules was investigated using an EGFR kinase assay, immunoprecipitation, western blotting, microarray analysis,quantitative polymerase chain reaction analysis, and measurement of lactate and ATP synthesis. Results: In the course of screening 30,000 substances, a reagent, âErtredin,â was found to inhibit anchorage-independent 3D growth of sphere-forming cells transfected with EGFRvIII cDNA. Ertredin also inhibited sphere formation in cells expressing wild-type EGFR in the presence of EGF. However, it did not affect anchorage-dependent 2D growth of parental NIH3T3 cells. The 3D-growth-inhibitory activity of some derivatives, including those with new structures, was similar to Ertredin. Furthermore, we demonstrated that Ertredin suppressed tumor growth in an allograft transplantation mouse model injected with EGFRvIII- or wild-type EGFR-expressing cells; a clear toxicity to host animals was not observed. Functional characterization of Ertredin in cells expressing EGFRvIII indicated that it stimulated EGFRvIII ubiquitination, suppressed both oxidative phosphorylation and glycolysis under 3D conditions, and promoted cell apoptosis. Conclusion: We developed a high throughput screening method based on anchorage-independent sphere formation induced by EGFRvIII-dependent transformation. In the course of screening, we identified Ertredin, which inhibited anchorage-independent 3D growth and tumor formation in nude mice. Functional analysis suggests that Ertredin suppresses both mitochondrial oxidative phosphorylation and cytosolic glycolysis in addition to promoting EGFRvIII degradation, and stimulates apoptosis in sphere-forming, EGFRvIII-overexpressing cells. Patterns of gene expression in cells treated with Ertredin (sample 2), rotenone (sample 3), and AG1478 (sample 4) were compared with vehicle-control cells (sample 1).
2016-08-01 | E-GEOD-76959 | biostudies-arrayexpress
Project description:To explore genes involved in epiblast development, we have employed whole genome microarray expression profiling as a discovery platform to identify genes. Embryoid body (EB) formation induces embryonic stem (ES) cells to differentiate into germ layers via epiblasts and extra-embryonic tissues, whereas ES cells give rise only to extra-embryonic tissues in monolayer culture. We compared gene expression profiles of ES cells in each differentiation culture methods at day 1-3 or 4 of differentiation. The expression of organizer related genes (Lhx1, Cer1 and Foxa2) was specifically induced at day 3 of EBs, but not in monolayer culture. In epiblast model cells, the overexpression of Lhx1 induced gene expression of organizer and meso-endodermal markers, suggested that Lhx1 was related to epiblast differentiation. Gene expression related epiblast development was measured at undifferentiated state and day 1-3 or 4 of differentiation. Two independent experiments were performed at each time using different people for each experiment.
2015-04-01 | E-GEOD-64715 | biostudies-arrayexpress
Project description:We found that human cord blood nucleated red blood cells (NRBCs) have a regulatory function in the innate immune reaction. NRBCs suppressed the production of inflammatory cytokines including TNF-a and IL-1b from monocytes in response to lipopolysaccharide (LPS). NRBCs exerted the regulatory function even without cell-to-cell contact with monocytes. On the other hand, IL-10 production from monocytes by the stimulation of LPS in the presence of NRBCs was higher than that of LPS-stimulated monocytes cultured in the absence of NRBCs. Addition of an anti-IL-10 receptor blocking antibody restored the inflammatory cytokine production from monocytes, suggesting that the functional change of monocytes caused by the interaction of NRBCs was characterized and mediated by the increased IL-10 production. Whole-genome microarray analysis revealed that monocytes expressed increased amounts of IL-10 superfamily genes after the interaction with NRBCs. IL-19, one of the IL-10 superfamily, enhanced IL-10 production from monocytes, which suggested cooperative role of IL-10 superfamily in the suppression of inflammatory cytokine production from monocytes. Arginase which was reported to play an important role in the suppressive function of NRBCs on monocytes in mice was found to play no significant role in human monocytes. NRBCs seem to have a regulatory role to suppress vigorous innate immune reaction which can be harmful to the fetuses via some unknown soluble factor which enhances the production of IL-10 and IL-10 family cytokines in monocytes. Human LPS-stimulated monocytes were collected after culture in a condition without and with NRBCs in transwell culture system. Only one experiment was performed.
2015-12-31 | E-GEOD-70146 | biostudies-arrayexpress
Project description:Carcinogenic bacteria, Helicobacter pylori, induce DNA double-strand breaks in infected host cells, while ATM-dependent DNA damage responses in host cells suppress genome instabilities caused by DNA breakages, which resulting in the suppression of H. pylori-induced gastric cancers. Although Helicobacter pylori infection is etiologically related to the inflammation-related malignancy, gastric cancers, it role in the molecular pathogenesis of disease remains unclear. In vitro studies have suggested the infection may cause breaks in double-stranded DNA. We used microarray analysis of H. pylori-infected human gastric biopsies to investigate the effect of H. pylori on gene expression genes involved in DNA repair and DNA damage response. Micro-array analysis and immunohistochemistory showed that ATM (ataxia-telangiectasia mutated) was upregulated in H. pylori gastritis but down regulated in the premalignant lesion, intestinal metaplasia. Studies in gastric cancer cell lines showed that H. pylori-infection induced activation of ATM and formation of γ-H2AX. γ-H2AX formation was present following infection with bout cag pathogenicity island (PAI)- positive and negative strains but more robust with cag PAI positive strains consistent with the fact that both cag PAI positive negative strains are associated with gastric cancer but the risk is higher with cag PAI positive strains. Eradication of H. pylori infection is associated with a reduction in cancer risk even in the most high risk populations. These data provide a plausible molecular mechanism for a direct bacterial-host interaction increasing cancer risk. To identify tumor suppressors affected by H. pylori-infection, microarray screening was used to compare the gene expression profiles of gastric mucosa obtained from individuals with H. pylori-gastritis and with intestinal metaplasia with tissue from uninfected controls.
2014-08-18 | E-GEOD-47797 | biostudies-arrayexpress