Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Distinct gene signatures define pathogen- versus diet-induced atherosclerosis development

ABSTRACT: The goal of this study was to define gene expression profiles in aortic tissue in response to three pro-atherogenic stimuli at two time points. We identified gene expression profiles induced by oral P.gingivalis (Pg), intranasal C. pneumoniae (Cp), and Western diet (WD) at acute (1 day after last infection, Pg, Cp, and control groups) and chronic (9 weeks after last infection, Pg, Cp, and control groups; WD for 9 weeks) time points in aortas of Apolipoprotein E (Apoe-/-) mice. 3 replicates per group were analyzed. RNA was analyzed using Mouse Gene 1.0 ST Array (Affymetrix, Santa Clara, CA). Total RNA from aortic tissue of Apoe-/- mice treated with P. gingivalis, C. pneumoniae, or fed a Western diet were compared to controls at acute and chronic time points.

ORGANISM(S): Mus musculus

SUBMITTER: Adam Gower

PROVIDER: E-GEOD-60086 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Publications

Distinct gene signatures in aortic tissue from ApoE-/- mice exposed to pathogens or Western diet.

Kramer Carolyn D CD Weinberg Ellen O EO Gower Adam C AC He Xianbao X Mekasha Samrawit S Slocum Connie C Beaulieu Lea M LM Wetzler Lee L Alekseyev Yuriy Y Gibson Frank C FC Freedman Jane E JE Ingalls Robin R RR Genco Caroline A CA

BMC genomics 20141224

<h4>Background</h4>Atherosclerosis is a progressive disease characterized by inflammation and accumulation of lipids in vascular tissue. Porphyromonas gingivalis (Pg) and Chlamydia pneumoniae (Cp) are associated with inflammatory atherosclerosis in humans. Similar to endogenous mediators arising from excessive dietary lipids, these Gram-negative pathogens are pro-atherogenic in animal models, although the specific inflammatory/atherogenic pathways induced by these stimuli are not well defined. I ...[more]

PMID: 25540039

Similar Datasets

Project description:Uncontrolled Transforming growth factor-beta (TGFβ) signaling promotes aggressive metastatic properties in late-stage breast cancers. However, how TGFβ-mediated cues are directed to induce late-stage tumorigenic events is poorly understood, particularly given that TGFβ has clear tumor suppressing activity in other contexts. Here we demonstrate that the transcriptional regulators TAZ and YAP (TAZ/YAP), key effectors of the Hippo pathway, are necessary to promote and maintain TGFβ-induced tumorigenic phenotypes in breast cancer cells. Interactions between TAZ/YAP, TGFβ-activated SMAD2/3, and TEAD transcription factors reveal convergent roles for these factors in the nucleus. Genome-wide expression analyses indicate that TAZ/YAP, TEADs and TGFβ-induced signals coordinate a specific pro-tumorigenic transcriptional program. Importantly, genes cooperatively regulated by TAZ/YAP, TEAD, and TGFβ, such as the novel targets NEGR1 and UCA1, are necessary for maintaining tumorigenic activity in metastatic breast cancer cells. Nuclear TAZ/YAP also cooperate with TGFβ signaling to promote phenotypic and transcriptional changes in non-tumorigenic cells to overcome TGFβ repressive effects. Our work thus identifies crosstalk between nuclear TAZ/YAP and TGFβ signaling in breast cancer cells, revealing novel insight into late-stage disease-driving mechanisms. Expression profiling was conducted following the repression of the transcriptional regulators TAZ and YAP (TAZ/YAP), the TEAD family of transcription factors (TEAD1/2/3/4), or the TGFb signaling pathway (with SB-431542, an inhibitor of the TBRI recpeptor) in human MDA-MB-231-LM2 breast cancer cells treated with TGFβ1. Human MDA-MB-231-LM2-4 breast cancer cells were transfected with control siRNA, or siRNAs targeting TAZ/YAP or all four TEADs and were treated 24 hours later with 500pM TGFβ1 or 5mM SB-431542 for an additional 24 hours. Total RNA was isolated and twelve microarrays in total were performed, with each condition carried out three times on separate days. The Boston University Microarray Core generated the data using the Affymetrix Human Gene 1.0 St Array.

Project description:Transcriptional profiling of Control and RbpjkCNULL lungs from E18.5. For microarray profiling, total RNA from E18.5 lungs was submitted for labeling and hybridization (Mouse Gene 1.0 ST Whole Genome Array, Affymetrix) to the Boston University Microarray Core facility. Clara cells (CCs) are a morphologically and operationally heterogeneous population of secretoglobin Scgb1a1-expressing secretory cells crucial for airway homeostasis and post-injury repair. Insights into the extent and origin of CC diversity have been hindered by the limited knowledge of markers of these cells and their precursors. To identify novel putative markers of CCs we characterized global changes in gene expression in embryonic lungs in which CCs were suppressed by conditional disruption of Notch signaling (Rbpjkcnull). Microarray profiling and Real Time PCR (qRT-PCR) identified eleven genes differentially downregulated in the E18.5 airways of Rbpjkcnull compared to controls, nearly half not previously known to mark CCs. Remarkably, in situ hybridization (ISH) revealed overlapping but also distinct domains of expression of these genes in E18.5 controls. Notably, Reg3g, Chad, Gabrp and Lrrc26 were selectively expressed in CCs of proximal airways and Upk3a expression was highly enriched in a CC subpopulation surrounding Neuroepithelial Bodies (NEBs). All genes expressed in the adult airways were found to be expressed in adult CCs and downregulated by selective CC ablation in a Naphthalene model of injury. Flow cytometry-based isolation of CCs from different airway regions of adult B1-EGFP reporter mice and qRT-PCR corroborated the spatial enrichment in gene expression observed by ISH. Remarkably, although, Scgb3a2, Upk3a, Cyp2f2, Cbr2, Krt15 could be detected unambiguously in airway progenitors as early as E14.5, only Scgb3a2 and Upk3a had their expression suppressed by disruption of Notch signaling, implicating both genes as the earliest markers for CC differentiation. Our study supports the idea that the diversification of the CC phenotype already arises during embryonic development and identifies candidate markers that can be used to investigate this process. Control (n=3) versus RbpjkCNULL(n=3)

Dataset Information

Distinct gene signatures define pathogen- versus diet-induced atherosclerosis development

Publications

Distinct gene signatures in aortic tissue from ApoE-/- mice exposed to pathogens or Western diet.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure