Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling by array of three-dimensional human bronchial epithelial cultures (MucilAir) treated with cigarette smoke, sodium hypochlorite (NaClO), tert-butyl hydroquinone (tBHQ), cisplatin, bleomycin, TNF-alpha, and IL-1beta.

ABSTRACT: Chronic obstructive pulmonary disease (COPD) is combination of progressive lung diseases. The diagnosis of COPD is generally based on the pulmonary function testing, however, difficulties underlie in prognosis of potential or early stage of COPD patients due to the complexity and heterogeneity of the pathogenesis. Transcriptomic technology is expected as one of the solution to resolve such complexities; therefore, we obtained transcriptomic data by in vitro testing with exposures of human 3D cultured bronchial epithelial tissues (MucilAir) to known inducible factors for early events of COPD to identify the potential descriptive marker genes. Fifteen potential biomarker genes were identified by transcriptomic analysis, and 10 out of 15 genes, as well as their coding proteins, have not been previously reported as biomarkers for chronic inflammatory lung diseases. The expression levels of these 15 genes with machine learning classification well distinguished between COPD and non-COPD patients with remarkable accuracy, suggesting these identified genes are potential descriptive marker genes for COPD.

ORGANISM(S): Homo sapiens

SUBMITTER: Kazushi Matsumura

PROVIDER: E-MTAB-7992 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:In vitro toxicology approaches have evolved, from a focus on the molecular changes within a cell to understanding of toxicity-related mechanisms that simulate the in vivo environment. The recent development of three dimensional (3-D) organotypic nasal epithelial culture models offer a physiologically robust system for studying the effects of exposure through inhalation. Exposure to cigarette smoke (CS) is associated with nasal inflammation; thus the nasal epithelium is relevant for evaluating the pathophysiological impact of CS exposure. The present study investigated further the relevancy and application of in vitro human 3-D nasal epithelial culture models for toxicological assessment of inhalation exposure. The biological impact was assessed following exposure to aerosol generated from a candidate modified risk tobacco product (MRTP), the Tobacco Heating System (THS) 2.2, as compared with smoke generated from reference cigarette 3R4F using an in vitro human 3-D nasal epithelial cultures. A series of experimental repetitions where multiple doses of the aerosol and smoke were applied, were conducted to obtain reproducible measurements and reliable observations to understand the cellular/molecular changes that occur following exposure. Aligned with the 3Rs Strategy and the Vision-and-Strategy of the Toxicity Testing in the 21st Century, this study implemented a systems toxicology approach and found that for all tested concentrations, the impact of 3R4F smoke was considerably greater than that of THS2.2 aerosol in terms of cytotoxicity levels, alterations in the tissue morphology, secretion of pro-inflammatory mediators, impaired ciliary function, and increased perturbed transcriptomes and miRNA expression profiles. In addition, to evaluate further the possible adverse effects of THS2.2 aerosol, a dose range assessment was conducted. A broader range of THS2.2 concentrations were exposed to the nasal cultures. Various dilutions of THS2.2 were applied to the cultures using the VitrocellÂ® 24/48 exposure system, corresponding to the concentrations of nicotine between 0.15 mg/L and 1.79 mg/L

Dataset Information

Transcription profiling by array of three-dimensional human bronchial epithelial cultures (MucilAir) treated with cigarette smoke, sodium hypochlorite (NaClO), tert-butyl hydroquinone (tBHQ), cisplatin, bleomycin, TNF-alpha, and IL-1beta.

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