MiRNA changes in mild and moderate emphysema correlate with target gene expression in vivo and in vitro
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ABSTRACT: This SuperSeries is composed of the following subset Series: GSE33336: Development of microRNA expression signature for emphysema in COPD patients GSE33337: miRNA changes in mild and moderate emphysema correlate with target gene expression in vivo and in vitro [target gene expression data] Refer to individual Series
Project description:To define the role of microRNAs and their mRNA targets in emphysema severity in COPD patients. We performed Agilent human miRNA oligo arrays (8x15K array, Part No. G4470A, Agilent Technologies) based on miRBase V9.1 on lung tissues from 9 mild and 20 moderate emphysema lungs obtained from patients undergoing curative resection for lung cancer. We identified 5 miRNAs and two of those were tested and validated technically using qRT-PCR. The predicted mRNA targets for the five miRNAs were identified in MSigDB using GSEA and their expression were negatively correlated in exvivo lung mRNA expression profile obtained from GEO datasets (GSE17770 and GSE1650). Increasing the expression of one of the miRNA target, miR-34c in BEAS-2B and HFL 1 cell lines resulted in the downregulation of 50 TargetScan and Pictar predicted targets of miR-34c.
Project description:To define the role of microRNAs and their mRNA targets in emphysema severity in COPD patients. We performed Agilent human miRNA oligo arrays (8x15K array, Part No. G4470A, Agilent Technologies) based on miRBase V9.1 on lung tissues from 9 mild and 20 moderate emphysema lungs obtained from patients undergoing curative resection for lung cancer. We identified 5 miRNAs and two of those were tested and validated technically using qRT-PCR. The predicted mRNA targets for the five miRNAs were identified in MSigDB using GSEA and their expression were negatively correlated in exvivo lung mRNA expression profile obtained from GEO datasets (GSE17770 and GSE1650). Increasing the expression of one of the miRNA target, miR-34c in BEAS-2B and HFL 1 cell lines resulted in the downregulation of 50 TargetScan and Pictar predicted targets of miR-34c.
Project description:This SuperSeries is composed of the following subset Series:; GSE14383: Effects of chronic exposure of human bronchial epithelial cells to low doses of cigarette smoke condensate; GSE14385: Response of bronchial epithelial cells to low doses of cigarette smoke condensate and subsequent demethylation agent Experiment Overall Design: Refer to individual Series
Project description:BEAS-2B cells have been treated with low doses (20 ug/ml) of CSC for 4 months. As negative control BEAS-2B cells were treated with DMSO (the CSC solvent). Non-treated cells were cultivated in parallel. Experiment Overall Design: After each month total RNA was extracted from three replicates of CSC, DMSO and non-treated BEAS-2B cells and hybridized to Affymetrix GeneChips.
Project description:Combined pulmonary fibrosis and emphysema (CPFE) is characterized by upper-lobe emphysema combined with lower-lobe fibrosis and a high prevalence of pulmonary hypertension. The aim of this study was to measure and analyze gene expression profiles in the lungs of CPFE patients. The results showed that the expression profiles of the fibrotic and emphysematous lesions were remarkably different in terms of function. Genes related to immune system, structural constituents of cytoskeleton, and cellular adhesion were overexpressed in fibrotic lesions, while genes associated with cellular fraction, cell membrane structures, vascular growth and biology, second-messenger-mediated signaling, and lung development (all processes that contribute to the destruction and repair of cells, vessels, and lung) were overexpressed in emphysematous lesions. The differences in gene expression were detected in fibrotic and emphysematous lesions in CPFE patients. We propose that the development of coexisted fibrotic and emphysematous lesions in CPFE is implemented by these different patterns of gene expressions. Lung tissue specimens from fibrous lesions and emphysematous lesions of 3 patients with combined pulmonary fibrosis and emphysema (CPFE) were obtained for RNA extraction and hybridization on Affymetrix microarrays. We hypothesized that coexisted fibrosis and emphysema in CPFE are programmed by differential gene expressions in the corresponding lesions in the lungs of smokers susceptible to CPFE. Given the importance of genetic susceptibility in understanding the etiology and pathogenesis of CPFE, we examined tissues from patients with CPFE to systemically identify genes significantly expressed in lung tissues with fibrotic lesions as well as genes significantly expressed in tissues with emphysematous lesions.
Project description:Human BEAS-2B bronchial epithelial cells were exposed directly at the air-liquid interphase towards exhaust gas and particles of a ship engine. The goal was to compare the responses towards different fuel combustions. The engine run either on diesel fuel (DF) or on Heavy Fuel Oil (HFO). The lung cells were exposed 3 times to each combustion aerosol (DF or HFO). The duration of the exposure was 4h. The cells were seeded into transwell-inserts 24h before exposure. Within each exposure 3 transwell-inserts were exposed to the complete aerosol and 3 transwell-inserts were exposed to the filtered aerosol. Effects of the complete aerosol were referenced against the filtered aerosol to determine the effects of the aerosol particles.
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 naïve 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(-/-).
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.
Project description:Amorphous silica nanoparticles induce malignant transformation and tumorigenesis of human lung epithelial cells. We used microarrays to detail the global programme of gene expression underlying the cellular malignant transformation induced by amorphous silica nanoparticles and identified distinct classes of up-regulated and down-regulated genes during this process. The human lung epithelial cells, Beas-2B were continuously exposed to 5 μg/mL amorphous silica nanoparticles for 40 passages, and named as BeasSiNPs-P40 (shortly as P40-5 during the further microarray detection). Meanwhile, the passage-matched control Beas-2B cells, named as Beas-P40 (shortly as NC during the further microarray detection).