Gene Expression Of TMEM178 Decreases With The Progression Of Asthma Severity

Abstract

The transmembrane protein 178 (Tmem178) is a novel negative regulator of the nuclear factor of activated T-cells, cytoplasmic 1 (NFAT1c); a recognized player in asthma pathogenesis. Our group has previously shown that changes in TMEM178 gene expression are associated with lower airway obstruction in asthmatics having an acute respiratory illness-induced exacerbation. We sought to compare the relative gene expression of TMEM178 in the airway epithelium of severe asthmatics to that in the airway epithelium of non-severe asthmatics and healthy controls. We performed a secondary analysis of two high-quality publicly available microarray datasets (National Center for Biotechnology Information’s Gene Expression Omnibus database; accession numbers GSE43696 and GSE63142), which contained epithelial brushings obtained by bronchoscopy from asthmatics and healthy donors. For differential gene expression comparisons, moderated Benjamini-Hochberg t-tests (with false discovery rate adjustments) and Dunn’s multiple comparison tests were used. In the first microarray study (GSE43696), severe asthmatics had significantly lower levels of TMEM178 gene expression when compared to moderate asthmatics (p-value <0.05) and healthy controls (p-value <0.0001). Similarly, in the second microarray study (GSE63142), severe asthmatics had significantly lower levels of TMEM178 gene expression when compared to non-severe asthmatics (p-value <0.001) and healthy controls (p-value <0.0001). Overall, TMEM178 gene expression negatively correlates with asthma severity. In two independent microarray studies, the relative gene expression of TMEM178 decreased with the progression of asthma severity. We speculate that Tmem178 may play an important role in the regulation of NFAT-induced inflammation in severe asthmatics.