GPR126 is an adhesion G protein‐coupled receptor which lies on chromosome 6q24. Genetic variants in this region are reproducibly associated with lung function and COPD in genome wide association studies (GWAS). The aims of this study were to define the role of GPR126 in the human lung and in pulmonary disease and identify possible casual variants. Online tools (GTEx and LDlink) identified SNPs which may have effects on GPR126 function/ expression, including missense variant Ser123Gly and an intronic variant that shows eQTL effects on GPR126 expression. GPR126 signaling via cAMP‐mediated pathways was identified in human structural airway cells when activated with the tethered agonist, stachel. RNA‐seq was used to identify downstream genes/ pathways affected by stachel‐mediated GPR126 activation in human airway smooth muscle cells. We identified ~350 differentially expressed genes at 4 and 24 hours post stimulation with ~20% overlap. We identified that genes regulated by GPR126 activation include IL33, CTGF, and SERPINE1, which already have known roles in lung biology. Pathways altered by GPR126 included those involved in cell cycle progression and cell proliferation. Here, we suggest a role for GPR126 in airway remodeling.

A single solvent‐based film casting process for fabricating porous polymer films is developed in this study. The porous film is produced by mixing concentrated polylactic acid (PLA)/chloroform solution (20 wt%) and fresh chloroform solvent is followed by film casting. The average pore sizes of the films produced are seen to increase from 2.1 (±0.1) µm to 6.4 (±0.2) µm with increasing ratio of concentrated PLA solution and fresh solvent from 1:2 to 1:4. Functional groups of PLA after casting into porous film are confirmed via Fourier transform infrared spectroscopy analysis. Cytocompatibility studies (via Alamar Blue assessment) utilizing MG‐63 cells on the porous PLA films reveal an increase in cell metabolic activity up to 8 d postseeding. In addition, these direct cell culture studies show that the porous membranes support cell adhesion and growth not only on the surface but also through the porous structures of the membrane, highlighting the suitability of these porous films in tissue engineering applications.

Genome wide association (GWA) studies have reproducibly identified signals on chromosome 4q24 associated with lung function and COPD. GSTCD (Glutathione S -transferase C-terminal domain containing) represents a candidate causal gene in this locus, however little is currently known about the function of this protein. We set out to further our understanding of the role of GSTCD in cell functions and homeostasis using multiple molecular and cellular approaches in airway relevant cells. Recombinant expression of human GSTCD in conjunction with a GST activity assay did not identify any enzymatic activity for two GSTCD isoforms questioning the assignment of this protein to this family of enzymes. Protein structure analyses identified a potential methyltransferase domain contained within GSTCD, with these enzymes linked to cell viability and apoptosis. Targeted knockdown (siRNA) of GSTCD in bronchial epithelial cells identified a role for GSTCD in cell viability as proliferation rates were not altered. To provide greater insight we completed transcriptomic analyses on cells with GSTCD expression knocked down and identified several differentially expressed genes including those implicated in airway biology; fibrosis e.g. TGFBR1 and inflammation e.g. IL6R . Pathway based transcriptomic analyses identified an over-representation of genes related to adipogenesis which may suggest additional functions for GSTCD. These findings identify potential additional functions for GSTCD in the context of airway biology beyond the hypothesised GST activity and warrant further investigation.