Differential global gene expression in cystic fibrosis nasal and bronchial epithelium

Abstract

Respiratory epithelium is the target of therapies, such as gene therapy, for cystic fibrosis (CF) lung disease. To determine the usefulness of the nasal epithelium as a pre-screen for lung-directed therapies, we profiled gene expression in CF and non-CF nasal and bronchial epithelium samples using Illumina HumanRef-8 Expression BeadChips. 863 genes were differentially expressed between CF and non-CF bronchial epithelium but only 15 were differentially expressed between CF and non-CF nasal epithelium (≥1.5-fold, P≤0.05). The most enriched pathway in CF bronchial epithelium was inflammatory response, whereas in CF nasal epithelium it was amino acid metabolism. We also compared nasal and bronchial epithelium in each group and identified differential expression of cellular movement genes in CF patients and cellular growth genes in non-CF subjects. We conclude that CF and non-CF nasal and bronchial epithelium are transcriptionally distinct and CF nasal epithelium is not a good surrogate for the lung respiratory epithelium.

Long noncoding RNA are aberrantly expressed in vivo in the cystic fibrosis bronchial epithelium

“…These results are concordant with the known inflammatory nature of the CF lung and show a similar profile to that found by others (Ogilvie et al, 2011). For example, target of Myb1 (TOM1) is a negative regulator of TLR2/4 signalling, that is significantly up-regulated in CF bronchial epithelial cells (Oglesby et al, 2010); TOM1 mRNA expression was also increased in the CF samples tested in this study (data not shown).…”

“…Other studies have profiled mRNA expression within the context of CF. At least three studies have profiled mRNA expression in the CF nasal epithelium (Ogilvie et al, 2011, Wright et al, 2006, Clarke et al, 2013.…”

“…Differences between studies may be partly explained by different experimental procedures employed. These differences include genotype of the cells used, statistical or normalisation approaches and tissue type; such as bronchial and nasal brushings (Ogilvie et al, 2011, Wright et al, 2006, Clarke et al, 2013, isogenic bronchial cells (Virella-Lowell et al, 2000), primary tracheal and bronchial cell cultures (Zabner et al, 2005) and foetal tracheal cells (Verhaeghe et al, 2007). It remains to be determined what direct contribution mutant CFTR makes to an altered CF transcriptome, and it is highly likely that other factors such as infection and inflammation are major contributors to this altered expression of both lncRNAs and protein coding transcripts.…”

High-Content siRNA Screen Reveals Global ENaC Regulators and Potential Cystic Fibrosis Therapy Targets

“…Accordingly, the nine genes in class VII ( Figure 3B), i.e., whose siRNA no longer inhibit ENaC under aprotinin nor under Nedd4-2-siRNA, could be related to such crosstalk: KCNQ3, TAS2R1, TNFRSF1B, B4GALT6, KIFAP3, CDK10, GRINA, SCGB3A1, and IFIH1 (Dataset S4). One of these (SCGB3A1) is downregulated in CF nasal epithelium (Clarke et al, 2013) and CF bronchial epithelium (Ogilvie et al, 2011) and upregulated during air-liquid interface differentiation of human bronchial epithelial cells (Ross et al, 2007).…”

Transcriptome meta-analysis reveals common differential and global gene expression profiles in cystic fibrosis and other respiratory disorders and identifies CFTR regulators

“…Besides our own nasal epithelial cell study (Clarke et al 2013), we chose 2 other CF data sets, one measuring gene expression in bronchial epithelial brushings (Ogilvie et al 2011), and one in foetal tracheal cell lines (Verhaeghe et al 2007). We added other studies measuring gene expression in chronic lung diseases, namely chronic obstructive pulmonary disorder (COPD: Bhattacharya et al 2009), idiopathic pulmonary fibrosis (IPF: Meltzer et al 2011) and asthma (Kicic et al 2010),…”