当前位置： SCI文献检索 > BMC Pulmonary Medicine期刊下所有文献 > Gene expression analysis in asthma using a targeted multiplex array.

Gene expression analysis in asthma using a targeted multiplex array.

Abstract：

BACKGROUND:Gene expression changes in the structural cells of the airways are thought to play a role in the development of asthma and airway hyperresponsiveness. This includes changes to smooth muscle contractile machinery and epithelial barrier integrity genes. We used a targeted gene expression arrays to identify changes in the expression and co-expression of genes important in asthma pathology. METHODS:RNA was isolated from the airways of donor lungs from 12 patients with asthma (8 fatal) and 12 non-asthmatics controls and analyzed using a multiplexed, hypothesis-directed platform to detect differences in gene expression. Genes were grouped according to their role in airway dysfunction: airway smooth muscle contraction, cytoskeleton structure and regulation, epithelial barrier function, innate and adaptive immunity, fibrosis and remodeling, and epigenetics. RESULTS:Differential gene expression and gene co-expression analyses were used to identify disease associated changes in the airways of asthmatics. There was significantly decreased abundance of integrin beta 6 and Ras-Related C3 Botulinum Toxin Substrate 1 (RAC1) in the airways of asthmatics, genes which are known to play an important role in barrier function. Significantly elevated levels of Collagen Type 1 Alpha 1 (COL1A1) and COL3A1 which have been shown to modulate cell proliferation and inflammation, were found in asthmatic airways. Additionally, we identified patterns of differentially co-expressed genes related to pathways involved in virus recognition and regulation of interferon production. 7 of 8 pairs of differentially co-expressed genes were found to contain CCCTC-binding factor (CTCF) motifs in their upstream promoters. CONCLUSIONS:Changes in the abundance of genes involved in cell-cell and cell-matrix interactions could play an important role in regulating inflammation and remodeling in asthma. Additionally, our results suggest that alterations to the binding site of the transcriptional regulator CTCF could drive changes in gene expression in asthmatic airways. Several asthma susceptibility loci are known to contain CTCF motifs and so understanding the role of this transcription factor may expand our understanding of asthma pathophysiology and therapeutic options.

journal_name

BMC Pulm Med

journal_title

BMC pulmonary medicine

authors

Pascoe CD,Obeidat M,Arsenault BA,Nie Y,Warner S,Stefanowicz D,Wadsworth SJ,Hirota JA,Jasemine Yang S,Dorscheid DR,Carlsten C,Hackett TL,Seow CY,Paré PD

doi

10.1186/s12890-017-0545-9

subject

Has Abstract

pub_date

2017-12-11 00:00:00

pages

189

issue

issn

1471-2466

pii

10.1186/s12890-017-0545-9

journal_volume

pub_type

杂志文章

在线工具

Gene expression analysis in asthma using a targeted multiplex array.