Gene expression changes in aortas of db/db versus control db/+ mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE6733 | GEO | 2011/12/23
SECONDARY ACCESSION(S): PRJNA98963
REPOSITORIES: GEO
Similar Datasets
Project description:To determine effects of hyperglycemia and insulin resistance on arterial wall biology, aortic gene expression profiles were generated using aortas from Lepr^db/db and their respective nondiabetic Lepr^db/+ controls. Keywords: Chip Experiment was done in triplicate with three independent pool of test Lepr^db/db and control Lepr^db/+ pooled samples. For RNA isolation aortas were striped of adventitia and periaortic fat. RNA from six aortas was pooled for the synthesis of probe for affymetrix array analysis.
2011-12-23 | E-GEOD-6733 | biostudies-arrayexpress
Project description:To determine effects of hyperglycemia and insulin resistance on arterial wall biology, gene expression profiles were generated using aortas from mice on high fat (35% fat) diet and their respective non diabetic regular chow fed controls. Keywords: Chip
2011-12-23 | GSE6735 | GEO
Project description:To determine effects of hyperglycemia and insulin resistance on arterial wall biology, gene expression profiles were generated using aortas from mice on high fat (35% fat) diet and their respective non diabetic regular chow fed controls. Keywords: Chip Experiment was done in triplicate with three independent pools from test mice on high fat diet and control mice on regular chow diet. For RNA isolation aortas were striped of adventitia and periaortic fat. RNA from three aortas was pooled for the synthesis of probe for affymetrix array analysis.
2011-12-23 | E-GEOD-6735 | biostudies-arrayexpress
Project description:Transcriptional profiling of mouse white adipose tissues. The objective of this study is to explore gene expression profiles of obese adipose tissue by DNA microarray data analysis. Male db/db (BKS.Cg-m+/+ Lepr db/J, 6 weeks old) and db/+ (BKS.Cg-Dock7m +/+ Lepr db/J, 6 weeks old) mice were used in this experiment.
2015-09-01 | E-GEOD-70527 | biostudies-arrayexpress
Project description:B-cell leukemia 11b (BCL11B) is a transcription factor known as an essential regulator of T lymphocytes and neuronal development during embryogenesis. A genome-wide association study (GWAS) showed that a gene desert region downstream of BCL11B, known to function as a BCL11B enhancer, harbors single nucleotide polymorphisms (SNPs) associated with increased arterial stiffness. However, a role for BCL11B in the adult cardiovascular system is unknown. Based on these human findings, we sought to examine the relation between BCL11B and arterial function. Here we report that BCL11B is expressed in the vascular smooth muscle (VSM) where it regulates vascular stiffness. RNA sequencing of aortas from WT and Bcl11b null mice (BSMKO) identified the cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) as the most significant differentially regulated signaling pathway in BSMKO compared to WT mice. BSMKO aortas showed decreased levels of PKG1, increased levels of Ca++-calmodulin-dependent serine/threonine phosphatase calcineurin (PP2B) and their common phosphorylation target, vasodilator-stimulated phosphoprotein (pVASPS239), a regulator of cytoskeletal actin rearrangements. Decreased pVASPS239 in BSMKO aortas was associated with increased actin polymerization (F/G actin ratio). Functionally, aortic force, stress, wall tension and stiffness, measured ex vivo in organ baths, were increased in BSMKO aortas, and BSMKO mice had increased pulse wave velocity, the in vivo index of arterial stiffness. Despite having no effect on blood pressure or microalbuminuria, increased arterial stiffness in BSMKO mice was associated with increased incidence of cerebral microbleeds compared to age-matched WT littermates. In conclusion, we have identified VSM BCL11B as a crucial regulator of aortic smooth muscle function and a potential therapeutic target for vascular stiffness.
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Project description:A better understanding of the molecular mechanisms underlying the development and progression of diabetic neuropathy (DN) is essential for the design of mechanism-based therapies. We examined changes in global gene expression to define pathways regulated by diabetes in peripheral nerve. Microarray data for 24 week-old BKS db/db and db/+ mouse sciatic nerve were analyzed to define significantly differentially expressed genes (DEGs); DEGs were further used for functional enrichment analysis and network analysis to identify biological processes and pathways differentially regulated in the db/db nerve. Expression profile clustering was performed to identify co-expressed DEGs. A set of co-expressed lipid metabolism genes was used for promoter sequence analysis.We identified 4,017 DEGs; 2,122 genes were up-regulated and 1,895 genes were down-regulated in the db/db relative to the db+ samples. Over-represented biological processes identified by the functional enrichment analysis include cell cycle, lipid metabolic process, lipid transport, carbohydrate metabolic process, response to stress, apoptosis, axonogenesis and cell adhesion. Pathways regulated in the db/db nerve include lipid metabolism, carbohydrate metabolism, energy metabolism, PPAR signaling, apoptosis, and axon guidance. The majority of DEGs in the glycolysis, TCA cycle, oxidative phosphorylation, fatty acid metabolism, glycerolipid metabolism, mitochondrial fatty acid elongation, lipid transport, adipocytokine signaling, PPAR signaling, and apoptosis pathways are up-regulated, whereas most of the axonogenesis-related genes are down-regulated in db/db nerve. A network of DEGs based on their co-citation in literature identified regulatory relationship between Tnf-α and key genes from the regulated pathways. Promoter sequence analysis identified over-represented transcription factor binding site (TFBS) motifs in the promoter regions of twenty two co-expressed lipid metabolism-related genes suggesting coordinated regulation of these genes by multiple transcription factors (TF). Furthermore, TF binding to these TFBS and differentially regulated in our data are annotated with nervous system development and immune response suggesting possible co-regulation of lipid metabolism, nervous system development and stress response genes. Gene expression changes in our data are consistent with pathological characteristics observed in DN including axon degeneration and demyelination, and support existing hypotheses regarding hyperglycemia mediated nerve damage in DN. Our findings support the role of hyperglycemia-induced oxidative stress and ischemia in nerve injury. Our results also support the hypothesis of oxidized lipid-mediated nerve injury and increased mitochondrial oxidative stress in dyslipidemia. Moreover, our analyses revealed a possible co-regulation mechanism connecting hyperlipidemia, stress response and axonal degeneration. Microarray data for 24 week-old BKS db/db and db/+ mouse sciatic nerve were analyzed to define significantly differentially expressed genes
2011-02-18 | E-GEOD-27382 | biostudies-arrayexpress
Project description:We investigated the gene expression profiles of RNA isolated from kidney glomeruli from aged, 25 week old type-2 diabetic (db/db) and non-diabetic mice. In order to investigate the consequences of hyperglycemia on the pathogenesis and progression of diabetic nephropathy Kidney glomeruli from 3 diabetic and 3 non-diabetic, control mice were isolated and RNA purified for RNA-Seq analysis on the Illumina HiSeq 2000. The goal of the project was to generate comprehensive list of noncoding RNA genes differentially regulated between the two conditions in order to identify novel targets for further study.
2016-10-24 | E-GEOD-77717 | biostudies-arrayexpress
Project description:Fibulin-4 plays an essential role in elastic fiber formation, though it's exact function is unclear. Mice lacking the fibulin-4 gene develop cutis laxa with thoracic aortic aneurysms and have narrowed descending aortic diamaters, dying shortly after birth. Another model that disrupt elastic fiber formation, elastin gene knockeds, are also perinatally lethal and have narrowed descending aortas but do not develop thoracic aneurysms. We hypothesized that there may be altered gene expression to explain the altered anatomy based on aortic tissue location we observed, which may provide therapeutic target(s) Ascending and descending aortas of p0 mouse pups were dissected, pooled in groups of eight, and homogenized to isolate RNA and we used microarrays on the pooled samples to identify genes that had expression significantly changed.
2015-04-10 | E-GEOD-67707 | biostudies-arrayexpress
Project description:A better understanding of the molecular mechanisms underlying the development and progression of diabetic neuropathy (DN) is essential for the design of mechanism-based therapies. We examined changes in global gene expression to define pathways regulated by diabetes in peripheral nerve. Microarray data for 24 week-old BKS db/db and db/+ mouse sciatic nerve were analyzed to define significantly differentially expressed genes (DEGs); DEGs were further used for functional enrichment analysis and network analysis to identify biological processes and pathways differentially regulated in the db/db nerve. Expression profile clustering was performed to identify co-expressed DEGs. A set of co-expressed lipid metabolism genes was used for promoter sequence analysis.We identified 4,017 DEGs; 2,122 genes were up-regulated and 1,895 genes were down-regulated in the db/db relative to the db+ samples. Over-represented biological processes identified by the functional enrichment analysis include cell cycle, lipid metabolic process, lipid transport, carbohydrate metabolic process, response to stress, apoptosis, axonogenesis and cell adhesion. Pathways regulated in the db/db nerve include lipid metabolism, carbohydrate metabolism, energy metabolism, PPAR signaling, apoptosis, and axon guidance. The majority of DEGs in the glycolysis, TCA cycle, oxidative phosphorylation, fatty acid metabolism, glycerolipid metabolism, mitochondrial fatty acid elongation, lipid transport, adipocytokine signaling, PPAR signaling, and apoptosis pathways are up-regulated, whereas most of the axonogenesis-related genes are down-regulated in db/db nerve. A network of DEGs based on their co-citation in literature identified regulatory relationship between Tnf-α and key genes from the regulated pathways. Promoter sequence analysis identified over-represented transcription factor binding site (TFBS) motifs in the promoter regions of twenty two co-expressed lipid metabolism-related genes suggesting coordinated regulation of these genes by multiple transcription factors (TF). Furthermore, TF binding to these TFBS and differentially regulated in our data are annotated with nervous system development and immune response suggesting possible co-regulation of lipid metabolism, nervous system development and stress response genes. Gene expression changes in our data are consistent with pathological characteristics observed in DN including axon degeneration and demyelination, and support existing hypotheses regarding hyperglycemia mediated nerve damage in DN. Our findings support the role of hyperglycemia-induced oxidative stress and ischemia in nerve injury. Our results also support the hypothesis of oxidized lipid-mediated nerve injury and increased mitochondrial oxidative stress in dyslipidemia. Moreover, our analyses revealed a possible co-regulation mechanism connecting hyperlipidemia, stress response and axonal degeneration.
2011-02-18 | GSE27382 | GEO
Project description:Assembly of HSPGs in the liver is defective in diabetes mellitus. A major consequence is impaired clearance of post-prandial lipoproteins, which ordinarily depends on the binding of these particles to hepatic HSPGs. Impaired clearance leads to prolonged exposure of the arterial wall to these harmful lipoproteins. We pin-pointed suppression of NDST-1 in livers of type 1 diabetic rats as at least a partial explanation for defective HSPG assembly. Dr. Williams' lab examined glycan-related gene expression in the livers of three groups of mice: wild-type, ad-lib-fed type 2 diabetic mice (db/db), and calorically restricted db/db mice (caloric restriction was shown several years ago to correct their clearance of atherogenic post-prandial lipoproteins). The results will indicate the molecular basis for defective HSPG assembly in type 2 diabetes, which is a question of considerable medical importance. RNA preparations from mice livers (wild-type, ad-lib-fed type 2 diabetic mice, and calorically restricted mice) were sent to Microarray Core (E). The RNA was amplified, labeled, and hybridized to GLYCO_v3 microarrays.
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