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GSE6929
Rattus norvegicus
8 Downloadable Samples
Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Background and aims: There are considerable evidences demonstrating that angiogenesis and chronic inflammation are mutually dependent. However, although cirrhosis progression is characterized with a chronic hepatic inflammatory process, this connection is not sufficiently explored as a therapeutic strategy. Therefore, this study was aimed to assess the potential benefits of targeting angiogenesis in cirrhotic livers to modulate inflammation and fibrosis. For this purpose, we evaluate the therapeutic utility of angiogenesis inhibitors. Methods: The in vivo effects of angiogenesis inhibitors were monitored in liver of cirrhotic rats by measuring angiogenesis, inflammatory infiltrate, fibrosis, a-smooth muscle actin (a-SMA) accumulation, differential gene expression (by microarrays), and portal pressure. Results: Cirrhosis progression was associated with a significant enhancement of vascular density and expression of vascular endothelial growth factor-A (VEGF-A), angiopoietin-1, angiopoietin-2 and placental growth factor (PlGF) in cirrhotic livers. The newly formed hepatic vasculature expressed vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). Interestingly, the expression of these adhesion molecules correlated well with local inflammatory infiltrate. Livers of cirrhotic rats treated with angiogenesis inhibitors presented a significant decrease in hepatic vascular density, inflammatory infiltrate, a-SMA abundance, collagen expression and portal pressure. Conclusion: Angiogenesis inhibitors may offer a potential novel therapy for cirrhosis due to its multiple mechanisms of action against angiogenesis, inflammation and fibrosis in cirrhotic livers.
Publication Title
Antiangiogenic treatment with sunitinib ameliorates inflammatory infiltrate, fibrosis, and portal pressure in cirrhotic rats.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Histidine-rich glycoprotein (HRG) is a 75 kDa heparin-binding plasma protein which has been implicated in regulation of tumor angiogenesis and growth. To exert some of its biological functions, HRG acts on macrophages.This study was performed to assess changes in gene expression in peritoneal macrophages treated with HRG using oligonucleotide microarrays
Publication Title
Genetic deficiency in plasma protein HRG enhances tumor growth and metastasis by exacerbating immune escape and vessel abnormalization.
Sample Metadata Fields
Specimen part, Disease, Treatment, Time
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Clariom S Human array (clariomshuman)
Description
Patients relapsing with FLT3-ITD mutant acute myeloid leukemia (AML) after allogeneic hematopoietic cell transplantation (allo-HCT) have a one-year-survival below 20%. We observed that sorafenib increased IL-15 production by FLT3-ITD+-leukemia cells, which synergized with the allogeneic CD8+T-cell response, leading to long-term survival in murine and humanized FLT3-ITD+AML models. Using IL-15 deficiency in recipient tissues or leukemia cells, IL-15 production upon sorafenib-treatment could be attributed to leukemia cells. Sorafenib treatment-related IL-15 production caused an increase in CD8+CD107a+IFN-+ T-cells with features of longevity (Bcl-2high/reduced PD-1-levels), which eradicated leukemia in secondary recipients. Mechanistically, sorafenib reduced ATF4 expression, thereby blocking negative regulation of IRF7-activation, which enhances IL-15 transcription. Consistent with the mouse data, IL-15 and pIRF7 levels increased in leukemic blasts of FLT3-ITD+AML patients upon sorafenib treatment. Analysis of 130 patients with FLT3-ITD-mutant AML relapsing after allo-HCT showed the highest complete remission-rate and median overall-survival-rate in the sorafenib/donor lymphocyte infusion (DLI) group compared to all other groups (chemotherapy, chemotherapy/DLI, sorafenib alone). Our findings indicate that the synergism of DLI and sorafenib is mediated via reduced ATF4 expression, causing activation of the pIRF7/IL-15-axis in leukemia cells. The sorafenib/DLI strategy therefore has the potential for an immune-mediated cure of FLT3-ITD-mutant AML- relapse, an otherwise fatal complication after allo-HCT.
Publication Title
Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Gallus gallus
- 20 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
HD11 cells were stimulated with 1 ug/ml endotoxin from ST-798 for 1, 2, 4 and 8 hours
Publication Title
Unique genome-wide transcriptome profiles of chicken macrophages exposed to Salmonella-derived endotoxin.
Sample Metadata Fields
Cell line, Time
View Samples- Sus scrofa
- 16 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
The objective of the present investigation was to utilize the GeneChip Porcine Genome Array from Affymetrix possessing 20, 201 unique probe sets to identify differentially expressed genes during rapid trophoblastic elongation and attachment to the uterine surface in the pig. Identification and characterization of conceptus gene expression patterns during rapid trophoblastic elongation and attachment in the pig will provide a better understanding of the events required for successful implantation and embryonic survival.
Publication Title
Identification of differential gene expression during porcine conceptus rapid trophoblastic elongation and attachment to uterine luminal epithelium.
Sample Metadata Fields
No sample metadata fields
View Samples- Sus scrofa
- 22 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
Mouse bone marrow-derived macrophages (BMDM) grown in macrophage colony-stimulating factor (CSF-1) have been used widely in studies of macrophage biology and the response to toll-like receptor agonists. We investigated whether similar cells could be derived from the domestic pig. Cultivation of pig bone marrow cells for 5-7 days in presence of rhCSF-1 generated a pure population of BMDM that expressed the usual macrophage markers (CD14, CD16, CD163, CD172a), are potent phagocytic cells and produced tumor necrosis factor (TNF) in response to lipopolysaccharide (LPS). Bone marrow cells could be stored frozen and thawed, providing a renewable resource.
Publication Title
Pig bone marrow-derived macrophages resemble human macrophages in their response to bacterial lipopolysaccharide.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Sus scrofa
- 8 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
BACKGROUND:
Publication Title
Endometrial gene expression profiling in pregnant Meishan and Yorkshire pigs on day 12 of gestation.
Sample Metadata Fields
Specimen part
View Samples- Sus scrofa
- 47 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
Transcriptional profiling coupled with blood metabolite analyses were used to identify porcine genes and pathways that respond to a fasting treatment or to a D298N missense mutation in the melanocortin-4 receptor (MC4R) gene. Gilts (12 homozygous for D298 and 12 homozygous for N298) were either fed ad libitum or fasted for 3 days. Fasting decreased body weight and backfat and increased serum concentrations of non-esterified fatty acid and urea. In response to fasting, 7,029 genes in fat and 1,831 genes in liver were differentially expressed (DE, q value less than 0.05). MC4R genotype did not affect gene expression, body weight, backfat depth, and any measured serum metabolite concentration. Pathway analyses of fasting-induced DE genes indicated that both liver and fat down-regulated energetically costly processes such as lipid and steroid synthesis and up-regulated efficient energy utilization pathways. Fasting increased expression of genes in involved in glucose sparing pathways in liver and extracellular matrix pathways in adipose tissue. Within the DE genes, transcription factors (TF) that regulate many DE genes were identified, confirming the involvement of TF that are known to regulate fasting response and implicating additional TF that are not known to be involved in energy homeostatic responses. Interestingly, estrogen receptor 1 transcriptionally controls fasting induced genes in fat that are involved in cell matrix morphogenesis. Our findings indicate a transcriptional response to fasting in two key metabolic tissues of pigs that was corroborated by changes in blood metabolites; and involvement of novel putative transcriptional regulators in the immediate adaptive response to fasting.
Publication Title
Microarray gene expression profiles of fasting induced changes in liver and adipose tissues of pigs expressing the melanocortin-4 receptor D298N variant.
Sample Metadata Fields
No sample metadata fields
View Samples- Sus scrofa
- 40 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
Residual feed intake (RFI) is a measure of feed efficiency, where low RFI denotes high feed efficiency. Caloric restriction (CR) is associated with feed efficiency in livestock species and to human health benefits such as longevity and cancer prevention. We have developed pig lines that differ in RFI and are interested to identify the genes and pathways that underlie feed efficiency. Prepubertal Yorkshire gilts with low RFI (n=10) or high RFI (n=10) were fed ad libitum or at 80% of maintenance for eight days. We measured serum metabolites and generated transcriptional profiles of liver and subcutaneous adipose tissue. 6,114 genes in fat and 305 genes in liver were differentially expressed (DE) in response to CR and 311 in fat and 147 in liver were DE due to RFI differences. Pathway analyses of CR-induced DE genes indicated a switch to a conservation mode of energy by down-regulating lipogenesis and steroidogenesis in both liver and fat. Interestingly, CR in pigs altered expression of genes in immune and cell cycle/apoptotic pathways in fat, which may explain part of the CR-driven lifespan enhancement. In-silico analysis of transcription factors revealed ESR1 as a putative regulator of the adaptive response to CR and several targets of ESR1 in our DE fat genes were annotated as cell cycle/apoptosis genes. Lipid metabolic pathway was overrepresented by down-regulated genes due to both CR and low RFI. We propose a common energy conservation mechanism, which may be controlled by PPARA, PPARG, and/or CREB in both CR and feed efficient pigs.
Publication Title
Gene expression profiling of the short-term adaptive response to acute caloric restriction in liver and adipose tissues of pigs differing in feed efficiency.
Sample Metadata Fields
Age, Specimen part
View Samples- Sus scrofa
- 14 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
A first generation Affymetrix GeneChip Porcine genome array was used to profile the gene expression in porcine mesenteric lymph nodes over a time course of infection with S. Typhimurium, including the acute (8 hours post inoculation (hpi), 24 hpi, 48 hpi) and chronic (21 days post-inoculation (dpi)) stages of infection. Our objectives were to 1) identify and examine the stereotypical gene expression response within host MLN to S. Typhimurium infection, 2) characterize global host responses by revealing the specific features of the hosts innate immunity pathways, and 3) explore if and how S. Typhimurium may escape the host immune response and develop into a carrier state.
Publication Title
Global transcriptional response of porcine mesenteric lymph nodes to Salmonella enterica serovar Typhimurium.
Sample Metadata Fields
Age
View Samples