Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Exploration of the genes affecting the compound acting against emphysema development in a mouse model of elastase-induced emphysema.

ABSTRACT: In a mouse model of elastase-induced emphysema, the effect of tetomilast against the emphysema development observed in C57BL/6J (C57) could be also detected in phosphodiesterase (PDE) 4D(+/+) but not in PDE4B(+/+), PDE4B(-/-), and PDE4D(-/-) mice. Based on this result, we hypothesized that the difference in the efficacy of tetomilast among these strains of mice might result from the differences in the levels of the target molecules of tetomilast other than PDE4 in each mouse strain. To test this hypothesis, we used microarrays to compare the expression levels of genes in the lungs of each mouse strain. The expression profiling by array demonstrated that the levels of cyclin-dependent kinase inhibitor 1 (CDKN1a) in PDE4B(+/+), PDE4B(-/-), and PDE4D(-/-) were higher than those in C57 and PDE4D(+/+).

ORGANISM(S): Mus musculus

PROVIDER: GSE85962 | GEO | 2016/08/24

SECONDARY ACCESSION(S): PRJNA339841

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Exploration of the genes affecting the compound acting against emphysema development in a mouse model of elastase-induced emphysema.

Project description:In a mouse model of elastase-induced emphysema, the effect of tetomilast against the emphysema development observed in C57BL/6J (C57) could be also detected in phosphodiesterase (PDE) 4D(+/+) but not in PDE4B(+/+), PDE4B(-/-), and PDE4D(-/-) mice. Based on this result, we hypothesized that the difference in the efficacy of tetomilast among these strains of mice might result from the differences in the levels of the target molecules of tetomilast other than PDE4 in each mouse strain. To test this hypothesis, we used microarrays to compare the expression levels of genes in the lungs of each mouse strain. The expression profiling by array demonstrated that the levels of cyclin-dependent kinase inhibitor 1 (CDKN1a) in PDE4B(+/+), PDE4B(-/-), and PDE4D(-/-) were higher than those in C57 and PDE4D(+/+). Total RNAs were extracted from the lungs from naÃ¯ve mice in each strain [C57, PDE4B(+/+), PDE4B(-/-), PDE4D(+/+), and PDE4D(-/)], and were used for microarray. In comparison with the expression levels of genes in C57, we retrieved the genes which expressed at the same levels in PDE4D(+/+), and at the different levels in PDE4B(+/+), PDE4B(-/-), and PDE4D(-/-).

2016-08-24 | E-GEOD-85962 | biostudies-arrayexpress

Eosinophils promote lung emphysema via CTSL

Project description:Patients with chronic obstructive pulmonary disease (COPD) having higher blood eosinophil levels exhibit worse lung function and more severe emphysema, implying the potential role of eosinophils in emphysema development. However, the specific mechanism underlying eosinophil-mediated emphysema development is not fully elucidated. In this study, single-cell RNA sequencing was used to identify eosinophil subgroups in mouse models of asthma and emphysema and analyze their functions. Analysis of the accumulated eosinophils revealed differential transcriptomes between the mouse lungs of elastase-induced emphysema and ovalbumin-induced asthma., Eosinophil depletion alleviated elastase-induced emphysema. Notably, eosinophil-derived cathepsin L (CTSL) degraded the extracellular matrix (ECM), causing emphysema in the pulmonary tissue. Eosinophils were positively correlated with serum CTSL levels, which were increased in patients with emphysema than in those without emphysema. Collectively, these results suggest that CTSL expression in eosinophils plays an important role in ECM degradation and remodeling and is related to emphysema in patients with COPD. Therefore, eosinophil-derived CTSL may serve as a potential therapeutic target for patients with emphysema.

2023-10-17 | GSE237749 | GEO

Testosterone deficiency altered mortality and the expression profile of protease inhibitors in an elastase-induced mouse model of emphysema

Project description:To evaluate the effect of testosterone on the pathophysiology of COPD, we created porcine pancreas elastase (PPE)-induced emphysema mouse model in sham or orchiectomized (ORX) mice [sham/PBS, sham/PPE, ORX/PBS, and ORX/PPE]. We performed microarray analysis to compare the gene expression levels in the lungs of each mice group. The results demonstrated that the levels of genes encoding protease inhibitor activity in ORX/PPE mice were lower than those in sham/PPE mice.

2023-06-24 | GSE153148 | GEO

Defining the Phosphodiesterase Superfamily Members in Rat Brain Microvessels

2012-02-01 | GSE35285 | GEO

Defining the Phosphodiesterase Superfamily Members in Rat Brain Microvessels

Project description:A filtration method followed by microarray analyses allows PDE components to be identified in brain microvessels, and confirmed that PDE4D and PDE5A are the primary forms expressed in rat brain microvessels. Adult male F344 rats were sacrificed and blocks of the cerebral cortex and infratentorial areas were dissected. Microvessels were isolated using a filtration method, and total RNA was extracted. Two microarrays using four sample RNAs (microvessels from the cerebral cortex vs. microvessels from the infratentorial block) were included in the present study. Microarrays demonstrated that there were 16 PDE transcripts in the PDE superfamily, exhibiting quantifiable density in the microvessels.

2012-02-01 | E-GEOD-35285 | biostudies-arrayexpress

Emphysema Lung Tissue Gene Expression Profiling

Project description:Gene expression profiling of lung tissue from undiseased (NML), 'usual' emphysema (EML), and Alpha-1 Antitrypsin Deficiency-related emphysema (ADL). Keywords = Emphysema Keywords = COPD Keywords = Alpha-1 Antitrypsin Deficiency Keywords: ordered

2004-06-01 | GSE1122 | GEO

Expression Profiling Identifies Genes Involved in Emphysema

Project description:Chronic obstructive pulmonary disease (COPD) is a major public health problem. The aim of this study was to identify genes involved in emphysema severity in COPD patients. Gene expression profiling was performed on total RNA extracted from non-tumor lung tissue from 30 smokers with emphysema. Class comparison analysis based on gas transfer measurement was performed to identify differentially expressed genes. Genes were then selected for technical validation by quantitative reverse transcriptase-PCR (qRT-PCR) if also represented on microarray platforms used in previously published emphysema studies. Genes technically validated advanced to tests of biological replication by qRT-PCR using an independent test set of 62 lung samples. Class comparison identified 98 differentially expressed genes (p<0.01). Fifty-one of those genes had been previously evaluated in differentiation between normal and severe emphysema lung. qRT-PCR confirmed the direction of change in expression in 29 of the 51 genes and 11 of those validated, remaining significant at p<0.05. Biological replication in an independent cohort confirmed the altered expression of eight genes, with seven genes differentially expressed by greater than 1.3 fold, identifying these as candidate determinants of emphysema severity. Gene expression profiling of lung from emphysema patients identified seven candidate genes associated with emphysema severity including COL6A3, SERPINF1, ZNHIT6, NEDD4, CDKN2A, NRN1 and GSTM3.

2009-09-21 | GSE17770 | GEO

Molecular mechanisms of cigarette smoke-induced lung emphysema

Project description:Chronic obstructive pulmonary disease (COPD) is a complex pulmonary disorder primarily induced by cigarette smoking, and characterized by persistent airflow limitation. The mouse represents an important model for studying COPD pathologies such as lung emphysema. In this respect, a number of mechanistic studies have been performed, however the approaches were mostly focused on single gene analysis or characterization of cellular, inflammatory or histopathological changes without attempting a more comprehensive interpretation. In the present study we aimed at applying systems biology approach to identify genome-wide molecular mechanisms indicative of cigarette smoke (CS)-induced lung emphysema. The lung transcriptomes of five mouse models (C57BL/6, ApoE-/-, A/J, CD1, and Nrf2-/-), that are known to be susceptible to CS-induced emphysema development, were analyzed following prolonged (5-6 months) CS exposure. The investigation resulted in the confirmation of many existing mechanistic explanations underlying smoke-induced lung emphysema, including increased transcriptional activity of NF-?B, and increased levels of TNF-a, IFN-g, and IL-1b. More importantly, we predicted mechanisms without currently well-documented roles, including increased transcriptional activity of PU.1, STAT1, C/EBP, FOXM1, YY1 and N-cor, and increased IL-17 cytokine expression, and reduced protein expression of ITGB6 and CFTR. We also corroborated, by using targeted proteomic approaches, several predictions such as reduced expression of ITGB6 and increased expression of BRCA1, C/EBPs, PU.1, TNF-a, IL-1b or CSF2. We believe this study will provide more insights into better understanding of CS-induced molecular processes underlying emphysema development in mice that may eventually be relevant in humans.

2014-11-28 | E-MTAB-2756 | biostudies-arrayexpress

Upregulation of Expression of Matrix Metalloproteinases in Alveolar Macrophages of HIV1+ Smokers with Early Emphysema

Project description:HIV1+ smokers develop emphysema at an earlier age and with a higher incidence than HIV1- smokers. Based on the knowledge that human alveolar macrophages (AM) are capable of producing proteases that degrade extracellular matrix components, we hypothesized that upregulation of AM matrix metalloproteinases may be associated with the emphysema of HIV1+ smokers. To test this hypothesis, microarray analysis was used to screen which MMP genes were expressed by AM isolated by bronchoalveolar lavage (BAL) of HIV1+ smokers with early emphysema. For each of the MMP genes observed to be expressed (MMP-1, -2, -7, -9, -10, -12 and -14), TaqMan PCR was used to quantify the relative expression in AM from 4 groups of individuals: HIV1 healthy nonsmokers, HIV1- healthy smokers, HIV1- smokers with early emphysema and HIV1+ smokers with early emphysema. Strikingly, while AM gene expression of MMPs was higher in HIV1- individuals with emphysema in comparison with HIV1- healthy smokers, for the majority of the MMPs (-1, -7, -9, -10, -12), AM expression from HIV1+ smokers with early emphysema was significantly higher than HIV1- smokers with early emphysema. Consistent with these observations, HIV1+ individuals with early emphysema had higher levels of epithelial lining fluid MMPs (-2, -7, -9,-12) than the 3 HIV1 groups. Interestingly, the active forms of MMP-2, -9 and -12 were detected in epithelial lining fluid from HIV1+ individuals with early emphysema, but not in any of the other groups. Considering that the substrate specificity of the upregulated AM MMPs includes collagenases, gelatinases, matrilysins and elastase, these data suggest that upregulated AM MMP genes and activation of MMP proteins may contribute to the emphysema of HIV1+ individuals who smoke. Keywords: expression study Asymptomatic HIV+ smokers with early emphysema

2016-03-24 | E-GEOD-10038 | biostudies-arrayexpress

Upregulation of Expression of Matrix Metalloproteinases in Alveolar Macrophages of HIV1+ Smokers with Early Emphysema

2016-03-24 | GSE10038 | GEO