PT  - JOURNAL ARTICLE
AU  - Robert Hall
AU  - Michael Portelli
AU  - Ian Hall
AU  - Ian Sayers
TI  - Using transcriptomics to understand the potential functions of lung function associated gene, GPR126 in human airway smooth muscle cells
AID  - 10.1183/13993003.congress-2019.PA5410
DP  - 2019 Sep 28
TA  - European Respiratory Journal
PG  - PA5410
VI  - 54
IP  - suppl 63
4099  - http://erj.ersjournals.com/content/54/suppl_63/PA5410.short
4100  - http://erj.ersjournals.com/content/54/suppl_63/PA5410.full
SO  - Eur Respir J2019 Sep 28; 54
AB  - GPR126 lies on chromosome 6q24 and variants in this region are reproducibly associated with lung function and COPD in genome wide association studies (GWAS). Our aims were to determine the effects of GPR126 signalling in vitro and determine the downstream effects of GPR126 activation in human airway smooth muscle cells.GPR126 mRNA expression in the lung and airway cells was established using RNA-seq. To assess the downstream effects of GPR126 activation in human airway cells, we activated HASMs (n=4) with the GPR126 agonist, the stachel peptide in the presence and absence of PKA inhibitor, H89 to identify the PKA dependency of this response. Differential gene expression was analysed by RNA-seq. Pathway analysis was carried out with DAVID and Reactome.GPR126 mRNA is expressed in HASMs. Stachel peptide upregulated 206 genes at 4 hours (5%FDR) and 18 of these genes were still upregulated after pre-incubation with H89. Of the 308 downregulated genes, 7 were still downregulated after H89 treatment. A similar PKA dependency was observed at 24 hours for both induced and reduced gene expression in response to stachel peptide. H89 also influenced gene expression independent of the stachel response.Pathway analyses revealed that stachel activation upregulated genes in xenobiotic metabolism, HOX gene activation during differentiation, axon guidance and FOXO-mediated transcription. Downregulated genes are involved in MAPK signalling, cell death gene transcription and actin cytoskeleton regulation.We identify that HASMs respond to a GPR126 agonist with different transcriptome profiles at 4 and 24 hours and that this response is largely cAMP-PKA dependent.FootnotesCite this article as: European Respiratory Journal 2019; 54: Suppl. 63, PA5410.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).