Abstract:
BACKGROUND:Glucocorticoids act on the glucocorticoid receptor (GR; NR3C1) to resolve inflammation and, as inhaled corticosteroids (ICS), are the cornerstone of treatment for asthma. However, reduced efficacy in severe disease or exacerbations indicates a need to improve ICS actions. METHODS:Glucocorticoid-driven transcriptomes were compared using PrimeView microarrays between primary human bronchial epithelial (HBE) cells and the model cell lines, pulmonary type II A549 and bronchial epithelial BEAS-2B cells. RESULTS:In BEAS-2B cells, budesonide induced (≥2-fold, P ≤ 0.05) or, in a more delayed fashion, repressed (≤0.5-fold, P ≤ 0.05) the expression of 63, 133, 240, and 257 or 15, 56, 236, and 344 mRNAs at 1, 2, 6, and 18 h, respectively. Within the early-induced mRNAs were multiple transcriptional activators and repressors, thereby providing mechanisms for the subsequent modulation of gene expression. Using the above criteria, 17 (BCL6, BIRC3, CEBPD, ERRFI1, FBXL16, FKBP5, GADD45B, IRS2, KLF9, PDK4, PER1, RGCC, RGS2, SEC14L2, SLC16A12, TFCP2L1, TSC22D3) induced and 8 (ARL4C, FLRT2, IER3, IL11, PLAUR, SEMA3A, SLC4A7, SOX9) repressed mRNAs were common between A549, BEAS-2B and HBE cells at 6 h. As absolute gene expression change showed greater commonality, lowering the cut-off (≥1.25 or ≤ 0.8-fold) within these groups produced 93 induced and 82 repressed genes in common. Since large changes in few mRNAs and/or small changes in many mRNAs may drive function, gene ontology (GO)/pathway analyses were performed using both stringency criteria. Budesonide-induced genes showed GO term enrichment for positive and negative regulation of transcription, signaling, proliferation, apoptosis, and movement, as well as FOXO and PI3K-Akt signaling pathways. Repressed genes were enriched for inflammatory signaling pathways (TNF, NF-κB) and GO terms for cytokine activity, chemotaxis and cell signaling. Reduced growth factor expression and effects on proliferation and apoptosis were highlighted. CONCLUSIONS:While glucocorticoids repress mRNAs associated with inflammation, prior induction of transcriptional activators and repressors may explain longer-term responses to these agents. Furthermore, positive and negative effects on signaling, proliferation, migration and apoptosis were revealed. Since many such gene expression changes occurred in human airways post-ICS inhalation, the effects observed in cell lines and primary HBE cells in vitro may be relevant to ICS in vivo.
journal_name
BMC Med Genomicsjournal_title
BMC medical genomicsauthors
Mostafa MM,Rider CF,Shah S,Traves SL,Gordon PMK,Miller-Larsson A,Leigh R,Newton Rdoi
10.1186/s12920-018-0467-2subject
Has Abstractpub_date
2019-01-31 00:00:00pages
29issue
1issn
1755-8794pii
10.1186/s12920-018-0467-2journal_volume
12pub_type
杂志文章abstract:BACKGROUND:Gulf War Illness (GWI) is a complex multi-symptom disorder that affects up to one in three veterans of this 1991 conflict and for which no effective treatment has been found. Discovering novel treatment strategies for such a complex chronic illness is extremely expensive, carries a high probability of failur...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-015-0111-3
更新日期:2015-07-09 00:00:00
abstract:BACKGROUND:While BMPR2 mutation strongly predisposes to pulmonary arterial hypertension (PAH), only 20% of mutation carriers develop clinical disease. This finding suggests that modifier genes contribute to FPAH clinical expression. Since modifiers are likely to be common alleles, this problem is not tractable by tradi...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-1-45
更新日期:2008-09-29 00:00:00
abstract:BACKGROUND:Germline mutations in the folliculin (FLCN) gene are associated with the development of Birt-Hogg-Dubé syndrome (BHDS), a disease characterized by papular skin lesions, a high occurrence of spontaneous pneumothorax, and the development of renal neoplasias. The majority of renal tumors that arise in BHDS-affe...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-3-59
更新日期:2010-12-16 00:00:00
abstract:BACKGROUND:Infant birth weight is a complex quantitative trait associated with both neonatal and long-term health outcomes. Numerous studies have been published in which candidate genes (IGF1, IGF2, IGF2R, IGF binding proteins, PHLDA2 and PLAGL1) have been associated with birth weight, but these studies are difficult t...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-5-10
更新日期:2012-04-12 00:00:00
abstract:BACKGROUND:Novel tuberculosis (TB) vaccines recently tested in humans have been designed to boost immunity induced by the current vaccine, Mycobacterium bovis Bacille Calmette-Guérin (BCG). Because BCG vaccination is used extensively in infants, this population group is likely to be the first in which efficacy trials o...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-2-10
更新日期:2009-02-24 00:00:00
abstract:BACKGROUND:The Cancer Genome Atlas (TCGA) is an important data resource for cancer biologists and oncologists. However, a lack of bioinformatics expertise often hinders experimental cancer biologists and oncologists from exploring the TCGA resource. Although a number of tools have been developed for facilitating cancer...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-018-0381-7
更新日期:2018-08-08 00:00:00
abstract:BACKGROUND:Postmenopausal hormone therapy (HT) influences endogenous hormone concentrations and increases the risk of breast cancer. Gene expression profiling may reveal the mechanisms behind this relationship.Our objective was to explore potential associations between sex hormones and gene expression in whole blood fr...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-4-29
更新日期:2011-03-31 00:00:00
abstract:BACKGROUND:Glioblastoma is a complex multifactorial disorder that has swift and devastating consequences. Few genes have been consistently identified as prognostic biomarkers of glioblastoma survival. The goal of this study was to identify general and clinical-dependent biomarker genes and biological processes of three...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-4-49
更新日期:2011-06-07 00:00:00
abstract:BACKGROUND:DNA methylation levels will be important for detection of epigenetic effects. However, there are few reports showing sex-related differences in the sensitivity to DNA methylation. To evaluate their sex-related individual differences in the sensitivity to methylation rigorously, we performed a systematic anal...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-016-0217-2
更新日期:2016-08-26 00:00:00
abstract::During June 10-12, 2018, the International Conference on Intelligent Biology and Medicine (ICIBM 2018) was held in Los Angeles, California, USA. The conference included 11 scientific sessions, four tutorials, one poster session, four keynote talks and four eminent scholar talks that covered a wide range of topics rang...
journal_title:BMC medical genomics
pub_type: 社论
doi:10.1186/s12920-018-0448-5
更新日期:2019-01-31 00:00:00
abstract:BACKGROUND:Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies in humans. The average 5-year survival rate is one of the lowest among aggressive cancers, showing no significant improvement in recent years. When detected early, HNSCC has a good prognosis, but most patients present metast...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-1-56
更新日期:2008-11-11 00:00:00
abstract:BACKGROUND:The noninvasive prenatal diagnosis procedures that are currently used to detect genetic diseases do not achieve desirable levels of sensitivity and specificity. Recently, fetal methylated DNA biomarkers in maternal peripheral blood have been explored for the noninvasive prenatal detection of genetic disorder...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-5-26
更新日期:2012-06-18 00:00:00
abstract:BACKGROUND:Expression quantitative trait loci (eQTL) are genomic regions regulating RNA transcript expression levels. Genome-wide Association Studies (GWAS) have identified many variants, often in non-coding regions, with unknown functions and eQTL provide a possible mechanism by which these variants may influence obse...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-7-31
更新日期:2014-06-03 00:00:00
abstract:BACKGROUND:Testing strategies is crucial for genetics clinics and testing laboratories. In this study, we tried to compare the hit rate between solo and trio and trio plus testing and between trio and sibship testing. Finally, we studied the impact of extended family analysis, mainly in complex and unsolved cases. MET...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-020-00743-8
更新日期:2020-07-17 00:00:00
abstract:BACKGROUND:Childhood asthma is a syndrome composed of heterogeneous phenotypes; furthermore, intrinsic biologic variation among racial/ethnic populations suggests possible genetic ancestry variation in childhood asthma. The objective of the study is to identify clinically homogeneous asthma subphenotypes in a diverse s...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-018-0367-5
更新日期:2018-05-31 00:00:00
abstract:BACKGROUND:Recent advances in omics technologies have raised great opportunities to study large-scale regulatory networks inside the cell. In addition, single-cell experiments have measured the gene and protein activities in a large number of cells under the same experimental conditions. However, a significant challeng...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-017-0312-z
更新日期:2017-12-28 00:00:00
abstract:BACKGROUND:Methotrexate is one of the earliest cytotoxic drugs used in cancer therapy, and despite the isolation of multiple other folate antagonists, methotrexate maintains its significant role as a treatment for different types of cancer and other disorders. The usefulness of treatment with methotrexate is limited by...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-1-35
更新日期:2008-08-11 00:00:00
abstract:BACKGROUND:To get insight into molecular mechanisms underlying insulin resistance, we compared acute in vivo effects of insulin on adipose tissue transcriptional profiles between obese insulin-resistant and lean insulin-sensitive women. METHODS:Subcutaneous adipose tissue biopsies were obtained before and after 3 and ...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-5-9
更新日期:2012-04-03 00:00:00
abstract:BACKGROUND:Rhodesiense sleeping sickness is caused by infection with T. b rhodesiense parasites resulting in an acute disease that is fatal if not treated in time. The aim of this study was to understand the global impact of active T. b rhodesiense infection on the patient's immune response in the early and late stages...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-020-0666-5
更新日期:2020-01-30 00:00:00
abstract:BACKGROUND:Glaucoma is the largest cause of irreversible blindness affecting more than 60 million people globally. The disease is defined as a gradual loss of peripheral vision due to death of Retinal Ganglion Cells (RGC). The RGC death is largely influenced by the rate of aqueous humor production by ciliary processes ...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-016-0177-6
更新日期:2016-03-22 00:00:00
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journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-019-0615-3
更新日期:2019-11-27 00:00:00
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journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-3-58
更新日期:2010-12-15 00:00:00
abstract:BACKGROUND:Despite being caused by mutations in different genes, diseases in the same phenotypic series are clinically similar, as reported in Part I of this study. Here, in Part II, we hypothesized that the phenotypic series too might be clinically similar. Furthermore, on the assumption that gene mutations indirectly...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-020-00793-y
更新日期:2020-09-24 00:00:00
abstract:BACKGROUND:Urothelial carcinoma (UC) is characterized by nonrandom chromosomal aberrations, varying from one or a few changes in early-stage and low-grade tumors, to highly rearranged karyotypes in muscle-invasive lesions. Recent array-CGH analyses have shed further light on the genomic changes underlying the neoplasti...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-1-3
更新日期:2008-01-31 00:00:00
abstract:BACKGROUND:Images embedded in biomedical publications carry rich information that often concisely summarize key hypotheses adopted, methods employed, or results obtained in a published study. Therefore, they offer valuable clues for understanding main content in a biomedical publication. Prior studies have pointed out ...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-6-S3-S8
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Hypermethylation of promoter CpG islands with associated loss of gene expression, and hypomethylation of CpG-rich repetitive elements that may destabilize the genome are common events in most, if not all, epithelial cancers. METHODS:The methylation of 6,502 CpG-rich sequences spanning the genome was analyze...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-1-47
更新日期:2008-09-30 00:00:00
abstract:BACKGROUND:The gene expression profile of cytologically-normal bronchial airway epithelial cells has previously been shown to be altered in patients with lung cancer. Although bronchoscopy is often used for the diagnosis of lung cancer, its sensitivity is imperfect, especially for small and peripheral suspicious lesion...
journal_title:BMC medical genomics
pub_type: 杂志文章,多中心研究
doi:10.1186/s12920-015-0091-3
更新日期:2015-05-06 00:00:00
abstract:BACKGROUND:The rapid adoption of next-generation sequencing provides an efficient system for detecting somatic alterations in neoplasms. The detection of such alterations requires a matched non-neoplastic sample for adequate filtering of non-somatic events such as germline polymorphisms. Non-neoplastic tissue adjacent ...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-016-0226-1
更新日期:2016-10-19 00:00:00
abstract:BACKGROUND:Loss of heterozygosity (LOH) is a common genetic event in cancer development, and is known to be involved in the somatic loss of wild-type alleles in many inherited cancer syndromes. The wider involvement of LOH in cancer is assumed to relate to unmasking a somatically mutated tumour suppressor gene through ...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-015-0123-z
更新日期:2015-08-01 00:00:00
abstract:BACKGROUND:While most pediatric sarcomas respond to front-line therapy, some bone sarcomas do not show radiographic response like soft-tissue sarcomas (rhabdomyosarccomas) but do show 90% necrosis. Though, new therapies are urgently needed to improve survival and quality of life in pediatric patients with sarcomas. Com...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-018-0456-5
更新日期:2019-01-31 00:00:00